Journal articles on the topic 'Liposomes Therapeutic use'
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1
Goins, Beth A., and William T. Phillips. "The Use of Scintigraphic Imaging During Liposome Drug Development." Journal of Pharmacy Practice 14, no. 5 (October 2001): 397–406. http://dx.doi.org/10.1106/da2m-fyju-1xxq-ppkk.
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Liposomes, spherical lipid bilayers enclosing an aqueous space, have become an important class of drug carriers. This review describes the usefulness of scintigraphic imaging during the development of liposome-based drugs. This imaging modality is particularly helpful for tracking the distribution of liposomes in the body, monitoring the therapeutic responses following administration of liposome-based drugs, and investigating the physiological responses associated with liposome administration. Scintigraphy also can be used to monitor the therapeutic responses of patients given approved liposomal drugs. Several examples describing the potential of this imaging modality during both the preclinical formulation and clinical trial stages of liposomal drug development are included. Techniques for radiolabeling liposomes as well as methods for producing scintigraphic images are also described.
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Cattel, Luigi, Maurizio Ceruti, and Franco Dosio. "From Conventional to Stealth Liposomes a new Frontier in Cancer Chemotherapy." Tumori Journal 89, no. 3 (May 2003): 237–49. http://dx.doi.org/10.1177/030089160308900302.
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Many attempts have been made to achieve good selectivity to targeted tumor cells by preparing specialized carrier agents that are therapeutically profitable for anticancer therapy. Among these, liposomes are the most studied colloidal particles thus far applied in medicine and in particular in antitumor therapy. Although they were first described in the 1960s, only at the beginning of 1990s did the first therapeutic liposomes appear on the market. The first-generation liposomes (conventional liposomes) comprised a liposome-containing amphotericin B, Ambisome (Nexstar, Boulder, CO, USA), used as an antifungal drug, and Myocet (Elan Pharma Int, Princeton, NJ, USA), a doxorubicin-containing liposome, used in clinical trials to treat metastatic breast cancer. The second-generation liposomes (“pure lipid approach”) were long-circulating liposomes, such as Daunoxome, a daunorubicin-containing liposome approved in the US and Europe to treat AIDS-related Kaposi's sarcoma. The third-generation liposomes were surface-modified liposomes with gangliosides or sialic acid, which can evade the immune system responsible for removing liposomes from circulation. The fourth-generation liposomes, pegylated liposomal doxorubicin, were called “stealth liposomes” because of their ability to evade interception by the immune system, in the same way as the stealth bomber was able to evade radar. Actually, the only stealth liposome on the market is Caelyx/Doxil (Schering-Plough, Madison NJ, USA), used to cure AIDS-related Kaposi's sarcoma, resistant ovarian cancer and metastatic breast cancer. Pegylated liposomal doxorubicin is characterized by a very long-circulation half-life, favorable pharmacokinetic behavior and specific accumulation in tumor tissues. These features account for the much lower toxicity shown by Caelyx in comparison to free doxorubicin, in terms of cardiotoxicity, vesicant effects, nausea, vomiting and alopecia. Pegylated liposomal doxorubicin also appeared to be less myelotoxic than doxorubicin. Typical forms of toxicity associated to it are acute infusion reaction, mucositis and palmar plantar erythrodysesthesia, which occur especially at high doses or short dosing intervals. Active and cell targeted liposomes can be obtained by attaching some antigen-directed monoclonal antibodies (Moab or Moab fragments) or small proteins and molecules (folate, epidermal growth factor, transferrin) to the distal end of polyethylene glycol in pegylated liposomal doxorubicin. The most promising therapeutic application of liposomes is as non-viral vector agents in gene therapy, characterized by the use of cationic phospholipids complexed with the negatively charged DNA plasmid. The use of liposome formulations in local-regional anticancer therapy is also discussed. Finally, pegylated liposomal doxorubicin containing radionuclides are used in clinical trials as tumor-imaging agents or in positron emission tomography.
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Deol, P., G. K. Khuller, and K. Joshi. "Therapeutic efficacies of isoniazid and rifampin encapsulated in lung-specific stealth liposomes against Mycobacterium tuberculosis infection induced in mice." Antimicrobial Agents and Chemotherapy 41, no. 6 (June 1997): 1211–14. http://dx.doi.org/10.1128/aac.41.6.1211.
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One recent promising development in the modification of drug formulations to improve chemotherapy is the use of a liposome-mediated drug delivery system. The efficacies of isoniazid and rifampin encapsulated in lung-specific stealth liposomes were evaluated by injecting liposomal drugs and free drugs into tuberculous mice twice a week for 6 weeks. Liposome-encapsulated drugs at and below therapeutic concentrations were more effective than free drugs against tuberculosis, as evaluated on the basis of CFUs detected, organomegaly, and histopathology. Furthermore, liposomal drugs had marginal hepatotoxicities as determined from the levels of total bilirubin and hepatic enzymes in serum. The elimination of mycobacteria from the liver and spleen was also higher with liposomal drugs than with free drugs. The encapsulation of antitubercular drugs in lung-specific stealth liposomes seems to be a promising therapeutic approach for the chemotherapy of tuberculosis.
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Xie, Yufei, Panagiota Papadopoulou, Björn de Wit, Jan C. d’Engelbronner, Patrick van Hage, Alexander Kros, and Marcel J. M. Schaaf. "Two Types of Liposomal Formulations Improve the Therapeutic Ratio of Prednisolone Phosphate in a Zebrafish Model for Inflammation." Cells 11, no. 4 (February 15, 2022): 671. http://dx.doi.org/10.3390/cells11040671.
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Glucocorticoids (GCs) are effective anti-inflammatory drugs, but their clinical use is limited by their side effects. Using liposomes to target GCs to inflammatory sites is a promising approach to improve their therapeutic ratio. We used zebrafish embryos to visualize the biodistribution of liposomes and to determine the anti-inflammatory and adverse effects of the GC prednisolone phosphate (PLP) encapsulated in these liposomes. Our results showed that PEGylated liposomes remained in circulation for long periods of time, whereas a novel type of liposomes (which we named AmbiMACs) selectively targeted macrophages. Upon laser wounding of the tail, both types of liposomes were shown to accumulate near the wounding site. Encapsulation of PLP in the PEGylated liposomes and AmbiMACs increased its potency to inhibit the inflammatory response. However, encapsulation of PLP in either type of liposome reduced its inhibitory effect on tissue regeneration, and encapsulation in PEGylated liposomes attenuated the activation of glucocorticoid-responsive gene expression throughout the body. Thus, by exploiting the unique possibilities of the zebrafish animal model to study the biodistribution as well as the anti-inflammatory and adverse effects of liposomal formulations of PLP, we showed that PEGylated liposomes and AmbiMACs increase the therapeutic ratio of this GC drug.
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Rahman, Mahfoozur, Sarwar Beg, Amita Verma, Imran Kazmi, Farhan Jalees Ahmed, Vikas Kumar, Firoz Anwar, and Sohail Akhter. "Liposomes as Anticancer Therapeutic Drug Carrier’s Systems: More than a Tour de Force." Current Nanomedicine 10, no. 2 (August 13, 2020): 178–85. http://dx.doi.org/10.2174/2468187309666190618171332.
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A liposome is a spherical vesicle composed of a bilayer of lipid with central aqueous cavity. Liposomes are the first nano vesicular drug delivery carriers, which are successfully translated into real-time clinical application and gained great potential in the past 30 years. The characteristics of liposomes to encapsulate both hydrophilic and hydrophobic drugs, their biocompatibility and biodegradability make it attractive nanocarriers in drug delivery area. Apart from this, great technical advancement has been made to develops second-generation liposomes named as stealth liposomes, cationic liposomes, triggered release liposomes and ligand targeted liposomes. This led to widespread use of liposomes in various areas including anticancer therapeutics, diagnostics and imaging agents. Therefore, the presents review article made an extensive discussion of various liposomes and its applications in cancer treatment.
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Roberts, Steven A., Chaebin Lee, Shrishti Singh, and Nitin Agrawal. "Versatile Encapsulation and Synthesis of Potent Liposomes by Thermal Equilibration." Membranes 12, no. 3 (March 11, 2022): 319. http://dx.doi.org/10.3390/membranes12030319.
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The wide-scale use of liposomal delivery systems is challenged by difficulties in obtaining potent liposomal suspensions. Passive and active loading strategies have been proposed to formulate drug encapsulated liposomes but are limited by low efficiencies (passive) or high drug specificities (active). Here, we present an efficient and universal loading strategy for synthesizing therapeutic liposomes. Integrating a thermal equilibration technique with our unique liposome synthesis approach, co-loaded targeting nanovesicles can be engineered in a scalable manner with potencies 200-fold higher than typical passive encapsulation techniques. We demonstrate this capability through simultaneous co-loading of hydrophilic and hydrophobic small molecules and targeted delivery of liposomal Doxorubicin to metastatic breast cancer cell line MDA-MB-231. Molecular dynamic simulations are used to explain interactions between Doxorubicin and liposome membrane during thermal equilibration. By addressing the existing challenges, we have developed an unparalleled approach that will facilitate the formulation of novel theranostic and pharmaceutical strategies.
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Khan, David R., Maggie N. Webb, Thomas H. Cadotte, and Madison N. Gavette. "Use of Targeted Liposome-based Chemotherapeutics to Treat Breast Cancer." Breast Cancer: Basic and Clinical Research 9s2 (January 2015): BCBCR.S29421. http://dx.doi.org/10.4137/bcbcr.s29421.
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The use of nanocarriers such as liposomes to deliver anticancer drugs to tumors can significantly enhance the therapeutic index of otherwise unencapsulated cytotoxic agents. This is in part because of the fact that the phospholipid bilayer can protect healthy sensitive tissue from the damaging effects of these types of drugs. Furthermore, the ease with which the phospholipid bilayer surface can be modified to allow for polyethylene glycol incorporation resulting in pegylated liposomes allow for increased circulation times in vivo, and thus an overall increase in the concentration of the drug delivered to the tumor site. This explains the clinical success of the liposomal-based drug Doxil, which has proven to be quite efficacious in the treatment of breast cancer. However, significant challenges remain involving poor drug transfer between the liposome and tumor cells with this type of nontargeted drug delivery system. Thus, future work involves the development of “smart” drugs, or targeted drug delivery intended for improved colocalization between the drug and cancerous cells. While it is not possible to entirely discuss such a rapidly growing field of study involving many different types of chemotherapeutics here, in this review, we discuss some of the recent advancements involving the development of targeted liposome-based chemotherapeutics to treat breast cancer.
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Amin, Mohamadreza, Mercedeh Mansourian, Peter C. Burgers, Bahareh Amin, Mahmoud Reza Jaafari, and Timo L. M. ten Hagen. "Increased Targeting Area in Tumors by Dual-Ligand Modification of Liposomes with RGD and TAT Peptides." Pharmaceutics 14, no. 2 (February 21, 2022): 458. http://dx.doi.org/10.3390/pharmaceutics14020458.
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Modification with polyethylene glycol (PEGylation) and the use of rigid phospholipids drastically improve the pharmacokinetics of chemotherapeutics and result in more manageable or reduced side-effects. A major drawback is retarded cellular delivery of content, which, along with tumor heterogeneity, are the two main obstacles against tumor targeting. To enhance cellular delivery and reach a bigger area of a tumor, we designed liposomes decorated with two ligands: one for targeting tumor vasculature via a cyclic-pentapeptide containing arginine-glycine-aspartic acid (RGD), which impacts tumor independent of passive accumulation inside tumors, and one for extravascular targeting of tumor cells via a cell-penetrating peptide derived from human immunodeficiency virus type 1 transactivator of transcription (TAT). Liposomes with different ligand combinations were prepared and compared with respect to performance in targeting. Intravital imaging illustrates the heterogeneous behavior of RGD-liposomes in both intravascular and extravascular distribution, whereas TAT-liposomes exhibit a predictable extravascular localization but no intravascular targeting. Dual-ligand modification results in enhanced vascular targeting and a predictable extravascular behavior that improves the therapeutic efficacy of doxorubicin-loaded liposomes but also an augmented clearance rate of liposomes. However, the dual-modified liposome could be a great candidate for targeted delivery of non-toxic payloads or contrast agents for therapeutic or diagnostic purposes. Here we show that the combination of vascular-specific and tumor cell-specific ligands in a liposomal system is beneficial in bypassing the heterogeneous expression of tumor-specific markers.
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Patel, Akshay Kumar, Shivanand K. Mutta, and Rajkumar Prasad Yadav. "Liposomes –A Overview." Asian Journal of Pharmaceutical Research and Development 9, no. 3 (June 15, 2021): 82–88. http://dx.doi.org/10.22270/ajprd.v9i3.934.
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Liposomes are sphere-shaped vesicles made up of one or more bilayers of phospholipids. The ability of delayed vesicles to transport medications, vaccines, diagnostic specialists, and other bioactive operators has accelerated development in the liposomal drug delivery system. The liposomal delivery system's pharmacyelements and pharmacokinetics properties have been altered, resulting in a higher therapeutic index and lower overall toxicity. There are many factors to consider, including size, size distribution, surface electrical potential, lamella count, and encapsulation efficacy. The use of surface modification in the development of liposomes with various mechanisms, kinetic properties, and biodistribution was discovered to be beneficial. Drug delivery, drug targeting, controlled release, and improved solubility have all been studied extensively with liposomes.
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Barros, Cecília de, Norberto Aranha, Patrícia Severino, Eliana B. Souto, Aleksandra Zielińska, André Lopes, Alessandra Rios, et al. "Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration." Pharmaceutics 13, no. 5 (May 10, 2021): 686. http://dx.doi.org/10.3390/pharmaceutics13050686.
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The therapeutic use of peptides has increasingly recognized in the development of new therapies. However, the susceptible enzymatic cleavage is a barrier that needs to overcome. Nose-to-brain delivery associated with liposomes can protect peptides against biodegradation and improve the accessibility to brain targets. The aim was to develop a liposomal formulation as ghrelin carrier. The quality by design (QbD) approach was used as a strategy for method development. The initial risk assessments were carried out using a fishbone diagram. A screening design study was performed for the critical material attributes/critical process parameters (CMAs/CPPs) on critical quality attributes (CQAs). Liposomes were obtained by hydrating phospholipid films, followed by extrusion or homogenization, and coated with chitosan. The optimized liposome formulation was produced by high-pressure homogenization coated with chitosan, and the resulted were liposomes size 72.25 ± 1.46 nm, PDI of 0.300 ± 0.027, the zeta potential of 50.3 ± 1.46 mV, and encapsulation efficiency of 53.2%. Moreover, chitosan coating improved performance in ex vivo permeation and mucoadhesion analyzes when compared to the uncoated liposome. In this context, chitosan coating is essential for the performance of the formulations in the ex vivo permeation and mucoadhesion analyzes. The intranasal administration of ghrelin liposomes coated with chitosan offers an innovative opportunity to treat cachexia.
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Kulikov, Oleg A., Valentin P. Ageev, Elena E. Marochkina, Irina S. Dolgacheva, Olga V. Minayeva, and Vera I. Inchina. "Efficacy of liposomal dosage forms and hyperosmolar salines in experimental pharmacotherapy of acute lung injury." Research Results in Pharmacology 5, no. 2 (June 26, 2019): 23–41. http://dx.doi.org/10.3897/rrpharmacology.5.35529.
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Introduction: Hypertonic sodium chloride solutions and liposomal drugs with pulmotropic effect are of great interest for the treatment of acute lung injury (ALI). The results of the studies on the efficacy of hypertonic solutions and liposomes in ALI treatment are currently controversial.Materials and methods: For the experiment, liposomes with dexamethasone, N-acetylcysteine (NAC), aprotinin and dye Cyanine-7 (Cy-7) were obtained. A liposome analysis was performed by means of spectrophotometry. ALI was modeled in rats by the administration of the damaging agents into the trachea. The experimental agents were injected once intravenously after the modeling of ALI. For experimental therapy used liposomal agents, 7.5% hypertonic saline (HS) and HyperHAES solutions in the respective groups. The efficacy of the therapy was assessed by the survival of animals, functional indicators of the cardiovascular and respiratory systems, and by the lung-body ratio. The biodistribution of liposomes after intravenous administration was investigated in mice through using a fluorescent dye Cy-7. The biodistribution of liposomes with Cy-7 was assessed using bioimaging according to the fluorescence intensity of internal organs (lungs, liver, and kidneys) and blood, expressed as dye concentration according to the calibration dependence of dye concentrarion on fluorescence intensity.Results and discussion: All the studied liposomal drugs were effective for the pharmacological correction of ALI. Hypertonic solutions, unlike liposomal drugs, were less likely to prevent the development of pulmonary edema. All the studied therapeutic agents increased the survival rate of the laboratory animals with ALI. The most effective experimental agent was liposomal dexamethasone. The use of drugs in form of simple liposomes with average diameter of 350 nm provided for a higher concentration of the drug in the lungs within the first 40 minutes after intravenous administration.Conclusion: Intravenous administration of liposomal forms is promising for the pharmacotherapy of acute lung injury.
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Cruz, Maria Eugénia Meirinhos, Maria Luísa Corvo, Maria Bárbara Martins, Sandra Simões, and Maria Manuela Gaspar. "Liposomes as Tools to Improve Therapeutic Enzyme Performance." Pharmaceutics 14, no. 3 (February 27, 2022): 531. http://dx.doi.org/10.3390/pharmaceutics14030531.
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The drugs concept has changed during the last few decades, meaning the acceptance of not only low molecular weight entities but also macromolecules as bioagent constituents of pharmaceutics. This has opened a new era for a different class of molecules, namely proteins in general and enzymes in particular. The use of enzymes as therapeutics has posed new challenges in terms of delivery and the need for appropriate carrier systems. In this review, we will focus on enzymes with therapeutic properties and their applications, listing some that reached the pharmaceutical market. Problems associated with their clinical use and nanotechnological strategies to solve some of their drawbacks (i.e., immunogenic reactions and low circulation time) will be addressed. Drug delivery systems will be discussed, with special attention being paid to liposomes, the most well-studied and suitable nanosystem for enzyme delivery in vivo. Examples of liposomal enzymatic formulations under development will be described and successful pre-clinical results of two enzymes, L-Asparaginase and Superoxide dismutase, following their association with liposomes will be extensively discussed.
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Vlasova, Kseniya Yu, Petr Ostroverkhov, Daria Vedenyapina, Tamara Yakimova, Alla Trusova, Galina Yurievna Lomakina, Stepan Sergeevich Vodopyanov, et al. "Liposomal Form of 2,4-Dinitrophenol Lipophilic Derivatives as a Promising Therapeutic Agent for ATP Synthesis Inhibition." Nanomaterials 12, no. 13 (June 23, 2022): 2162. http://dx.doi.org/10.3390/nano12132162.
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Mitochondrial uncoupler 2,4-dinitrophenol (2,4-DNP) is a promising antidiabetic and antiobesity agent. Its clinical use is limited by a narrow dynamic range and accumulation in non-target sensitive organs, which results in whole-body toxicity. A liposomal formulation could enable the mentioned drawbacks to be overcome and simplify the liver-targeted delivery and sustained release of 2,4-DNP. We synthesized 2,4-DNP esters with carboxylic acids of various lipophilic degrees using carboxylic acid chloride and then loaded them into liposomes. We demonstrated the effective increase in the entrapment of 2,4-DNP into liposomes when esters were used. Here, we examined the dependence of the sustained release of 2,4-DNP from liposomes on the lipid composition and LogPoct of the ester. We posit that the optimal chain length of the ester should be close to the palmitic acid and the lipid membrane should be composed of phospholipids with a certain phase transition point depending on the desired release rate. The increased effect of the ATP synthesis inhibition of the liposomal forms of caproic and palmitic acid esters compared to free molecules in liver hepatocytes was demonstrated. The liposomes’ stability could well be responsible for this result. This work demonstrates promising possibilities for the liver-targeted delivery of the 2,4-DNP esters with carboxylic acids loaded into liposomes for ATP synthesis inhibition.
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Inglut, Collin T., Aaron J. Sorrin, Thilinie Kuruppu, Shruti Vig, Julia Cicalo, Haroon Ahmad, and Huang-Chiao Huang. "Immunological and Toxicological Considerations for the Design of Liposomes." Nanomaterials 10, no. 2 (January 22, 2020): 190. http://dx.doi.org/10.3390/nano10020190.
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Liposomes hold great potential as gene and drug delivery vehicles due to their biocompatibility and modular properties, coupled with the major advantage of attenuating the risk of systemic toxicity from the encapsulated therapeutic agent. Decades of research have been dedicated to studying and optimizing liposomal formulations for a variety of medical applications, ranging from cancer therapeutics to analgesics. Some effort has also been made to elucidate the toxicities and immune responses that these drug formulations may elicit. Notably, intravenously injected liposomes can interact with plasma proteins, leading to opsonization, thereby altering the healthy cells they come into contact with during circulation and removal. Additionally, due to the pharmacokinetics of liposomes in circulation, drugs can end up sequestered in organs of the mononuclear phagocyte system, affecting liver and spleen function. Importantly, liposomal agents can also stimulate or suppress the immune system depending on their physiochemical properties, such as size, lipid composition, pegylation, and surface charge. Despite the surge in the clinical use of liposomal agents since 1995, there are still several drawbacks that limit their range of applications. This review presents a focused analysis of these limitations, with an emphasis on toxicity to healthy tissues and unfavorable immune responses, to shed light on key considerations that should be factored into the design and clinical use of liposomal formulations.
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Arpit Rajaram Suralkar, Chaitanya Shahaji Khedkar, Nidhi R Zanwar, Chanchal C Chandak, and Shital J Gandhi. "Liposomes as a novel drug delivery system." GSC Biological and Pharmaceutical Sciences 20, no. 3 (September 30, 2022): 336–43. http://dx.doi.org/10.30574/gscbps.2022.20.3.0372.
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Liposome is a microparticulate colloidal vesicle, in which aqueous medium is surrounded by single or multiple concentric layers of phospholipids. Both hydrophilic & hydrophobic drug can be incorporated, water soluble drug being trapped in aqueous core and fat soluble drug in phospholipids. It offers controlled release, targeted drug delivery thus enhanced therapeutic efficacy and reduced dosing frequency. Several liposome based drug formulation are approved for clinical use and many are under extensive investigation. Therapeutically, these are used as carrier for drugs, viruses, bacteria, antigen, peptides (antibiotic), vaccines, genes and diagnostic agents. This review discusses about the method of production and extensive therapeutic potential of liposomes as carriers for targeted and controlled delivery.
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Alwattar, Jana K., Amina T. Mneimneh, Kawthar K. Abla, Mohammed M. Mehanna, and Ahmed N. Allam. "Smart Stimuli-Responsive Liposomal Nanohybrid Systems: A Critical Review of Theranostic Behavior in Cancer." Pharmaceutics 13, no. 3 (March 8, 2021): 355. http://dx.doi.org/10.3390/pharmaceutics13030355.
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The epoch of nanotechnology has authorized novel investigation strategies in the area of drug delivery. Liposomes are attractive biomimetic nanocarriers characterized by their biocompatibility, high loading capacity, and their ability to reduce encapsulated drug toxicity. Nevertheless, various limitations including physical instability, lack of site specificity, and low targeting abilities have impeded the use of solo liposomes. Metal nanocarriers are emerging moieties that can enhance the therapeutic activity of many drugs with improved release and targeted potential, yet numerous barriers, such as colloidal instability, cellular toxicity, and poor cellular uptake, restrain their applicability in vivo. The empire of nanohybrid systems has shelled to overcome these curbs and to combine the criteria of liposomes and metal nanocarriers for successful theranostic delivery. Metallic moieties can be embedded or functionalized on the liposomal systems. The current review sheds light on different liposomal-metal nanohybrid systems that were designed as cellular bearers for therapeutic agents, delivering them to their targeted terminus to combat one of the most widely recognized diseases, cancer.
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Naik, Himgauri, Jafrin Jobayer Sonju, Sitanshu Singh, Ioulia Chatzistamou, Leeza Shrestha, Ted Gauthier, and Seetharama Jois. "Lipidated Peptidomimetic Ligand-Functionalized HER2 Targeted Liposome as Nano-Carrier Designed for Doxorubicin Delivery in Cancer Therapy." Pharmaceuticals 14, no. 3 (March 6, 2021): 221. http://dx.doi.org/10.3390/ph14030221.
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The therapeutic index of chemotherapeutic agents can be improved by the use of nano-carrier-mediated chemotherapeutic delivery. Ligand-targeted drug delivery can be used to achieve selective and specific delivery of chemotherapeutic agents to cancer cells. In this study, we prepared a peptidomimetic conjugate (SA-5)-tagged doxorubicin (Dox) incorporated liposome (LP) formulation (SA-5-Dox-LP) to evaluate the targeted delivery potential of SA-5 in human epidermal growth factor receptor-2 (HER2) overexpressed non-small-cell lung cancer (NSCLC) and breast cancer cell lines. The liposome was prepared using thin lipid film hydration and was characterized for particle size, encapsulation efficiency, cell viability, and targeted cellular uptake. In vivo evaluation of the liposomal formulation was performed in a mice model of NSCLC. The cell viability studies revealed that targeted SA-5-Dox-LP showed better antiproliferative activity than non-targeted Dox liposomes (Dox-LP). HER2-targeted liposome delivery showed selective cellular uptake compared to non-targeted liposomes on cancer cells. In vitro drug release studies indicated that Dox was released slowly from the formulations over 24 h, and there was no difference in Dox release between Dox-LP formulation and SA-5-Dox-LP formulation. In vivo studies in an NSCLC model of mice indicated that SA-5-Dox-LP could reduce the lung tumors significantly compared to vehicle control and Dox. In conclusion, this study demonstrated that the SA-5-Dox-LP liposome has the potential to increase therapeutic efficiency and targeted delivery of Dox in HER2 overexpressing cancer.
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Yang, Jieru, Farrhana Firdaus, Armira Azuar, Zeinab G. Khalil, Nirmal Marasini, Robert J. Capon, Waleed M. Hussein, Istvan Toth, and Mariusz Skwarczynski. "Cell-Penetrating Peptides-Based Liposomal Delivery System Enhanced Immunogenicity of Peptide-Based Vaccine against Group A Streptococcus." Vaccines 9, no. 5 (May 12, 2021): 499. http://dx.doi.org/10.3390/vaccines9050499.
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Peptide-based vaccine development represents a highly promising strategy for preventing Group A Streptococcus (GAS) infection. However, these vaccines need to be administered with the help of a delivery system and/or immune adjuvant. Cell-penetrating peptides (CPPs) have been used as a powerful tool for delivering various therapeutic agents, including peptides, as they can overcome the permeability barrier of cell membranes. Here, we used CPPs to deliver our lead lipopeptide-based vaccine (LCP-1). CPPs were anchored through a spacer to LCP-1-bearing multilamellar and unilamellar liposomes and administered to Swiss outbred mice. Tat47–57 conjugated to two palmitic acids via a (Gly)6 spacer (to form a liposome-anchoring moiety) was the most efficient system for triggering immune responses when combined with multilamellar liposomes bearing LCP-1. The immunostimulatory potential of a variety of other CPPs was examined following intranasal administration in mice. Among them, LCP-1/liposomes/Tat47–57 and LCP-1/liposomes/KALA induced the highest antibody titers. The antibodies produced showed high opsonic activity against clinically isolated GAS strains D3840 and GC2 203. The use of the CPP-liposome delivery system is a promising strategy for liposome-based GAS vaccine development.
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Fobian, Seth-Frerich, Ziyun Cheng, and Timo L. M. ten Hagen. "Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks." Pharmaceutics 14, no. 1 (December 23, 2021): 26. http://dx.doi.org/10.3390/pharmaceutics14010026.
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Cancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host’s immune capacity to eliminate tumors. Although some success has been seen in this field, toxicity and weak immune induction remain challenges. Liposomal nanosystems, previously used as targeting agents, are increasingly functioning as immunotherapeutic vehicles, with potential for delivery of contents, immune induction, and synergistic drug packaging. These systems are tailorable, multifunctional, and smart. Liposomes may deliver various immune reagents including cytokines, specific T-cell receptors, antibody fragments, and immune checkpoint inhibitors, and also present a promising platform upon which personalized medicine approaches can be built, especially with preclinical and clinical potentials of liposomes often being frustrated by inter- and intrapatient variation. In this review, we show the potential of liposomes in cancer immunotherapy, as well as the methods for synthesis and in vivo progression thereof. Both preclinical and clinical studies are included to comprehensively illuminate prospects and challenges for future research and application.
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Bang, Seung Hyuck, Simranjeet Singh Sekhon, Yang-Hoon Kim, and Jiho Min. "Preparation of liposomes containing lysosomal enzymes for therapeutic use." Biotechnology and Bioprocess Engineering 19, no. 5 (September 2014): 766–70. http://dx.doi.org/10.1007/s12257-014-0327-7.
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Mehta, Swapnil, Sanjay Kulkarni, Ajinkya N. Nikam, Bharat S. Padya, Abhijeet Pandey, and Srinivas Mutalik. "Liposomes as Versatile Platform for Cancer Theranostics: Therapy, Bio-imaging, and Toxicological Aspects." Current Pharmaceutical Design 27, no. 17 (June 17, 2021): 1977–91. http://dx.doi.org/10.2174/1381612827666210311142100.
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Liposomes are nano-sized formulations having the benefits of site-specificity, biocompatibility, and biodegradability, which make them useful for the therapy and diagnosis of major diseases like cancer. In this review, various synthetic strategies of liposomes and their biomedical application in special concern to cancer are discussed. In context to the biomedical application, this article gives a detailed insight into subcellular targeted therapy and several therapeutic modifications like immunotherapy, receptor-based therapy, phototherapy, and combination therapy. The review also describes the liposome-based imaging platforms and the toxicity associated with liposomes. Owing to a significant amount of benefits of this carrier system, several products have been approved to be launched in the market and several others have already been marketed for clinical use.
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Sinha, Roma, Jayeeta Roychoudhury, Partha Palit, and Nahid Ali. "Cationic Liposomal Sodium Stibogluconate (SSG), a Potent Therapeutic Tool for Treatment of Infection by SSG-Sensitive and -Resistant Leishmania donovani." Antimicrobial Agents and Chemotherapy 59, no. 1 (November 3, 2014): 344–55. http://dx.doi.org/10.1128/aac.03305-14.
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ABSTRACTPentavalent antimonials have been the first-line treatment for leishmaniasis for decades. However, the development of resistance to sodium stibogluconate (SSG) has limited its use, especially for treating visceral leishmaniasis (VL). The present work aims to optimize a cationic liposomal formulation of SSG for the treatment of both SSG-sensitive (AG83) and SSG-resistant (GE1F8R and CK1R)Leishmania donovaniinfections. Parasite killing was determined by the 3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium bromide (MTT) assay and microscopic counting of Giemsa-stained macrophages. Macrophage uptake studies were carried out by confocal microscopic imaging. Parasite-liposome interactions were visualized through transmission electron microscopy. Toxicity tests were performed using assay kits. Organ parasite burdens were determined by microscopic counting and limiting dilution assays. Cytokines were measured by enzyme-linked immunosorbent assays (ELISAs) and flow cytometry. Although all cationic liposomes studied demonstrated leishmanicidal activity, phosphatidylcholine (PC)-dimethyldioctadecylammonium bromide (DDAB) vesicles were most effective, followed by PC-stearylamine (SA) liposomes. Since entrapment of SSG in PC-DDAB liposomes demonstrated enhanced ultrastructural alterations in promastigotes, PC-DDAB-SSG vesicles were further investigatedin vitroandin vivo. PC-DDAB-SSG could effectively alleviate SSG-sensitive and SSG-resistantL. donovaniinfections in the liver, spleen, and bone marrow of BALB/c mice at a dose of SSG (3 mg/kg body weight) not reported previously. The parasiticidal activity of these vesicles was attributed to better interactions with the parasite membranes, resulting in direct killing, and generation of a strong host-protective environment, necessitating a very low dose of SSG for effective cures.
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Landucci, Elisa, Francesca Bonomolo, Chiara De Stefani, Costanza Mazzantini, Domenico Edoardo Pellegrini-Giampietro, Anna Rita Bilia, and Maria Camilla Bergonzi. "Preparation of Liposomal Formulations for Ocular Delivery of Thymoquinone: In Vitro Evaluation in HCEC-2 e HConEC Cells." Pharmaceutics 13, no. 12 (December 5, 2021): 2093. http://dx.doi.org/10.3390/pharmaceutics13122093.
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Thymoquinone (TQ) is the main constituent of Nigella sativa L. essential oil. In vitro studies have shown its protective effect against H2O2-induced oxidative stress in human retinal pigment epithelium cells, and in vivo experiments have demonstrated its effect in decreasing corneal neovascularization and reducing the inflammation in an experimental dry eye model in mice. Its therapeutic use is limited by poor bioavailability, low solubility, and scarce permeability. In this study, two liposomal formulations have been developed, both of which consist of phosphatidylcholine and Plurol Oleique, a liquid lipid, and one of which is coated with 0.1% w/v hyaluronic acid (HA) to increase both TQ solubility and its ocular therapeutic potential. Each formulation has a size <200 nm and an EE% around 70%, determined by scattering techniques and the HPLC-DAD analytical method, respectively, and they result in a 2-fold increase in TQ solubility. HA-coated liposomes are stable over 2 months at +4 °C, and coated and uncoated liposomes present a gradual and prolonged release of TQ. Two cell lines, human corneal epithelial cells (HCEC-2) and human conjunctival epithelial cells (HConEC) were used to investigate the safety of the liposomal formulations. Uptake studies were also performed using fluorescent liposomes. Both liposomes and, in particular, HA-coated liposomes reduce the TQ toxicity observed at high doses in both HCEC-2 and HConEC cells, and both formulations increase the absorption at the cellular level and especially at the nucleus level, with a more pronounced effect for HA-coated liposomes.
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Balazs, Daniel A., and WT Godbey. "Liposomes for Use in Gene Delivery." Journal of Drug Delivery 2011 (December 15, 2011): 1–12. http://dx.doi.org/10.1155/2011/326497.
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Liposomes have a wide array of uses that have been continuously expanded and improved upon since first being observed to self-assemble into vesicular structures. These arrangements can be found in many shapes and sizes depending on lipid composition. Liposomes are often used to deliver a molecular cargo such as DNA for therapeutic benefit. The lipids used to form such lipoplexes can be cationic, anionic, neutral, or a mixture thereof. Herein physical packing parameters and specific lipids used for gene delivery will be discussed, with lipids classified according to overall charge.
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Akhlaghi, Milad, Lida Eftekharivash, Mohammad Taebpour, Saeid Afereydoon, Marziyeh Ebrahimpour, Maryam Zarezadeh Mehrizi, Mahboobeh Zarezadeh Mehrizi, and Bibi fatemeh Haghirosadat. "Improving the Therapeutic Performance of Glycyrrhiza Glabra Hydroalcoholic Extract Using Liposomal Nano-carriers and Their Characterization." Disease and Diagnosis 11, no. 2 (April 1, 2022): 39–48. http://dx.doi.org/10.34172/ddj.2022.09.
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Background: The use of plants as therapeutic drugs has long been common among human beings. The Glycyrrhiza glabra is one of the medicinal plants with many therapeutic properties. However, using this herb in traditional methods faces some challenges. The use of pharmaceutical nano-carriers such as liposomes is one of the new strategies to overcome these challenges. In this regard, the current study aimed to synthesize and characterize liposomal nano-carriers containing the G. glabra hydroalcoholic extract to improve its therapeutic effects. Materials and Methods: After the extraction of the G. glabra root by the Soxhlet method, nano-liposomes containing G. glabra extracts were synthesized by the thin-film preparation method. Then, the encapsulation efficiency (EE) rate and drug release pattern of nanoliposome were examined using the spectrophotometry method. Next, physicochemical properties such as size, zeta potential, morphology, and non-interaction of the nano-system with the extract were investigated by dynamic-light-scattering (DLS), atomic force microscope (AFM), and Fourier transform infrared spectroscopy (FTIR) methods, and finally, the toxicity of the nano-system on human foreskin fibroblast cells was assessed using the MTT method. Results: Nano-liposomes containing licorice extracts with the EE of 2.3±75.32% were from the type of slow release and controlled release, having a size of 111.4±1.2 nm, a surface charge of -53.6±6.3, and a dispersion index of 0.210±0.13, and they had no interaction with the loaded extract. The results of the MTT test also demonstrated that the synthesized nano-liposomes were non-toxic on normal cells. Conclusion: Overall, the findings proved that synthesized nano-liposomes with proper physicochemical properties can be a suitable carrier for the G. glabra extract and thus cause stability and improve the therapeutic effects of this herbal extract as a medicinal plant.
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Duong, Thuan Thi, Antti Isomäki, Urve Paaver, Ivo Laidmäe, Arvo Tõnisoo, Tran Thi Hai Yen, Karin Kogermann, Ain Raal, Jyrki Heinämäki, and Thi-Minh-Hue Pham. "Nanoformulation and Evaluation of Oral Berberine-Loaded Liposomes." Molecules 26, no. 9 (April 29, 2021): 2591. http://dx.doi.org/10.3390/molecules26092591.
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Berberine (BBR) is a poorly water-soluble quaternary isoquinoline alkaloid of plant origin with potential uses in the drug therapy of hypercholesterolemia. To tackle the limitations associated with the oral therapeutic use of BBR (such as a first-pass metabolism and poor absorption), BBR-loaded liposomes were fabricated by ethanol-injection and thin-film hydration methods. The size and size distribution, polydispersity index (PDI), solid-state properties, entrapment efficiency (EE) and in vitro drug release of liposomes were investigated. The BBR-loaded liposomes prepared by ethanol-injection and thin-film hydration methods presented an average liposome size ranging from 50 nm to 244 nm and from 111 nm to 449 nm, respectively. The PDI values for the liposomes were less than 0.3, suggesting a narrow size distribution. The EE of liposomes ranged from 56% to 92%. Poorly water-soluble BBR was found to accumulate in the bi-layered phospholipid membrane of the liposomes prepared by the thin-film hydration method. The BBR-loaded liposomes generated by both nanofabrication methods presented extended drug release behavior in vitro. In conclusion, both ethanol-injection and thin-film hydration nanofabrication methods are feasible for generating BBR-loaded oral liposomes with a uniform size, high EE and modified drug release behavior in vitro.
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Parvathaneni, Vineela, Nishant S. Kulkarni, Snehal K. Shukla, Pamela T. Farrales, Nitesh K. Kunda, Aaron Muth, and Vivek Gupta. "Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment." Pharmaceutics 12, no. 3 (February 28, 2020): 206. http://dx.doi.org/10.3390/pharmaceutics12030206.
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Non-small cell lung cancer (NSCLC) is a global disorder, treatment options for which remain limited with resistance development by cancer cells and off-target events being major roadblocks for current therapies. The discovery of new drug molecules remains time-consuming, expensive, and prone to failure in safety/efficacy studies. Drug repurposing (i.e., investigating FDA-approved drug molecules for use against new indications) provides an opportunity to shorten the drug development cycle. In this project, we propose to repurpose pirfenidone (PFD), an anti-fibrotic drug, for NSCLC treatment by encapsulation in a cationic liposomal carrier. Liposomal formulations were optimized and evaluated for their physicochemical properties, in-vitro aerosol deposition behavior, cellular internalization capability, and therapeutic potential against NSCLC cell lines in-vitro and ex-vivo. Anti-cancer activity of PFD-loaded liposomes and molecular mechanistic efficacy was determined through colony formation (1.5- to 2-fold reduction in colony growth compared to PFD treatment in H4006, A549 cell lines, respectively), cell migration, apoptosis and angiogenesis assays. Ex-vivo studies using 3D tumor spheroid models revealed superior efficacy of PFD-loaded liposomes against NSCLC, as compared to plain PFD. Hence, the potential of inhalable liposome-loaded pirfenidone in NSCLC treatment has been established in-vitro and ex-vivo, where further studies are required to determine their efficacy through in vivo preclinical studies followed by clinical studies.
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Maroof, Alam, Mohammad Farazuddin, and Mohammad Owais. "Potential use of liposomal diallyl sulfide in the treatment of experimental murine candidiasis." Bioscience Reports 30, no. 4 (March 12, 2010): 223–31. http://dx.doi.org/10.1042/bsr20090068.
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In the present study, we evaluated the potential of a liposomal formulation of the garlic oil component DAS (diallyl sulfide) in treating disseminated infection caused by the intracellular opportunistic pathogen Candida albicans in experimental mice. The PC (phosphatidylcholine) liposomal formulation of DAS was evaluated for size, ζ-potential, entrapment efficiency and release kinetics, toxicity etc. For therapeutic studies, mice were challenged with intravenous infection dosage of 107 blastospores of C. albicans followed by treatment with various doses of DAS formulations [12 and 6 mg/kg b.w. (body mass)] three times, on alternative days. The antifungal efficacy of liposomal DAS was assessed on the basis of survival of treated mice as well as the residual fungal load in vital organs like liver and spleen of mice. The results of the present study showed that treatment with DAS-bearing liposomes (12 mg/kg b.w.) resulted in the highest survival rate in animals. Liposomal DAS also significantly decreased residual fungal load in vital organs of experimental animals compared with the free form of DAS. The liposomal DAS was also found to be free of toxic manifestations as revealed by the erythrocyte lysis test and liver/kidney function tests. The results of the present study established that the antifungal activity of DAS, a poorly soluble compound, can be enhanced by the incorporation of it into liposomes. Further studies and optimizations are needed to build upon the promising findings of this study to enable the development of an effective plant-derived antifungal formulation that can provide an alternative to currently available antifungal drugs.
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Alanazi, Saleh Ayed, Gamaleldin Ibrahim Harisa, Mohammad M. Badran, Nazrul Haq, Awwad Abdoh Radwan, Ashok Kumar, Faiyaz Shakeel, and Fars Kaed Alanazi. "Cholesterol-Conjugate as a New Strategy to Improve the Cytotoxic Effect of 5-Fluorouracil on Liver Cancer: Impact of Liposomal Composition." Current Drug Delivery 17, no. 10 (October 29, 2020): 898–910. http://dx.doi.org/10.2174/1567201817666200211095452.
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Purpose: Hepatocellular carcinoma (HCC) is a common liver malignancy, which has a low survival rate of all cancers. 5-fluorouracil (5-FU) is clinically recognized to treat HCC. However, the success of this therapy is highly limited due to rapid clearance and non- selective distribution. Cholesterol- conjugate (5-FUC) loaded liposomes proposed to facilitate the transport of 5-FUC into tumor cells via Low-Density Lipoprotein receptor (LDL receptor) that overexpressed in HCC. Thus, the aim of this study was to use 5-FUC loaded liposome as a promising strategy to combat HCC and improve the response of HCC to chemotherapy. Methods: 5-FUC and 5-FU loaded liposomes were optimized based on Cholesterol (CHO) ratio and type of phospholipid to achieve a potential effect on HCC. Liposomes were prepared by the thin-film hydration method, and evaluated in terms of particle size, polydispersity, zeta potential, Entrapment Efficiency (EE), morphology, drug release and cytotoxicity. Results: The obtained liposomes had a suitable nano-range particle size with negative zeta potential, and acceptable EE%. In vitro drug release of 5-FUC loaded liposomes showed a lower cumulative release over 24 h as compared to 5-FU loaded liposomes. 5-FUC loaded liposomes exhibited a higher in vitro cytotoxic effect as compared to the free drug and 5-FU loaded liposomes against HepG2 cell lines after 48 h via MTT assay. Conclusion: These results concluded that 5-FUC loaded liposomes could be used as an alternative tactic to increase the therapeutic index of 5-FU and pave the way for potential clinical applications.
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Schiffelers, Raymond M., Gert Storm, Marian T. ten Kate, and Irma A. J. M. Bakker-Woudenberg. "Therapeutic Efficacy of Liposome-Encapsulated Gentamicin in Rat Klebsiella pneumoniae Pneumonia in Relation to Impaired Host Defense and Low Bacterial Susceptibility to Gentamicin." Antimicrobial Agents and Chemotherapy 45, no. 2 (February 1, 2001): 464–70. http://dx.doi.org/10.1128/aac.45.2.464-470.2001.
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ABSTRACT Long-circulating liposomes (LCL) may be used as targeted antimicrobial drug carriers as they localize at sites of infection. As a result, LCL-encapsulated gentamicin (LE-GEN) has demonstrated superior antibacterial activity over the free drug in a single-dose study of immunocompetent rats with Klebsiella pneumoniaepneumonia. In the present study, the therapeutic efficacy of LE-GEN was evaluated by monitoring rat survival and bacterial counts in blood and lung tissue in clinically relevant models, addressing the issue of impaired host defense and low bacterial antibiotic susceptibility. The results show that in immunocompetent rats infected with the high-GEN-susceptibility K. pneumoniae strain, a single dose of LE-GEN is clearly superior to an equivalent dose of free GEN. Yet complete survival can also be obtained with multiple doses of free GEN. In leukopenic rats infected with the high-GEN-susceptible K. pneumoniae strain, free GEN at the maximum tolerated dose (MTD) was needed to obtain survival. However, with the addition of a single dose of LE-GEN to free-GEN treatment, complete survival can be obtained using a sevenfold-lower cumulative amount of GEN than with free-GEN treatment alone. In leukopenic rats infected with low-GEN-susceptibleK. pneumoniae cells, free GEN at the MTD did not result in survival. The use of LE-GEN is needed for therapeutic success. Increasing LE-GEN bilayer fluidity resulted in an increased GEN release from the liposomes and hence improved rat survival, thus showing the importance of the liposome lipid composition for therapeutic efficacy. These results warrant further clinical studies of liposomal formulations of aminoglycosides in immunocompromised patients with severe infections.
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He, Hua, Dongfen Yuan, Yun Wu, and Yanguang Cao. "Pharmacokinetics and Pharmacodynamics Modeling and Simulation Systems to Support the Development and Regulation of Liposomal Drugs." Pharmaceutics 11, no. 3 (March 7, 2019): 110. http://dx.doi.org/10.3390/pharmaceutics11030110.
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Liposomal formulations have been developed to improve the therapeutic index of encapsulated drugs by altering the balance of on- and off-targeted distribution. The improved therapeutic efficacy of liposomal drugs is primarily attributed to enhanced distribution at the sites of action. The targeted distribution of liposomal drugs depends not only on the physicochemical properties of the liposomes, but also on multiple components of the biological system. Pharmacokinetic–pharmacodynamic (PK–PD) modeling has recently emerged as a useful tool with which to assess the impact of formulation- and system-specific factors on the targeted disposition and therapeutic efficacy of liposomal drugs. The use of PK–PD modeling to facilitate the development and regulatory reviews of generic versions of liposomal drugs recently drew the attention of the U.S. Food and Drug Administration. The present review summarizes the physiological factors that affect the targeted delivery of liposomal drugs, challenges that influence the development and regulation of liposomal drugs, and the application of PK–PD modeling and simulation systems to address these challenges.
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Rango, Enrico, Fabio Pastorino, Chiara Brignole, Arianna Mancini, Federica Poggialini, Salvatore Di Maria, Claudio Zamperini, et al. "The Pyrazolo[3,4-d]Pyrimidine Derivative Si306 Encapsulated into Anti-GD2-Immunoliposomes as Therapeutic Treatment of Neuroblastoma." Biomedicines 10, no. 3 (March 12, 2022): 659. http://dx.doi.org/10.3390/biomedicines10030659.
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Si306, a pyrazolo[3,4-d]pyrimidine derivative recently identified as promising anticancer agent, has shown favorable in vitro and in vivo activity profile against neuroblastoma (NB) models by acting as a competitive inhibitor of c-Src tyrosine kinase. Nevertheless, Si306 antitumor activity is associated with sub-optimal aqueous solubility, which might hinder its further development. Drug delivery systems were here developed with the aim to overcome this limitation, obtaining suitable formulations for more efficacious in vivo use. Si306 was encapsulated in pegylated stealth liposomes, undecorated or decorated with a monoclonal antibody able to specifically recognize and bind to the disialoganglioside GD2 expressed by NB cells (LP[Si306] and GD2-LP[Si306], respectively). Both liposomes possessed excellent morphological and physio-chemical properties, maintained over a period of two weeks. Compared to LP[Si306], GD2-LP[Si306] showed in vitro specific cellular targeting and increased cytotoxic activity against NB cell lines. After intravenous injection in healthy mice, pharmacokinetic profiles showed increased plasma exposure of Si306 when delivered by both liposomal formulations, compared to that obtained when Si306 was administered as free form. In vivo tumor homing and cytotoxic effectiveness of both liposomal formulations were finally tested in an orthotopic animal model of NB. Si306 tumor uptake resulted significantly higher when encapsulated in GD2-LP, compared to Si306, either free or encapsulated into untargeted LP. This, in turn, led to a significant increase in survival of mice treated with GD2-LP[Si306]. These results demonstrate a promising antitumor efficacy of Si306 encapsulated into GD2-targeted liposomes, supporting further therapeutic developments in pre-clinical trials and in the clinic for NB.
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Utreja, Puneet, Shivani Verma, Mahfoozur Rahman, and Lalit Kumar. "Use of Nanoparticles in Medicine." Current Biochemical Engineering 6, no. 1 (March 12, 2020): 7–24. http://dx.doi.org/10.2174/2212711906666190724145101.
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Background: Nanotechnology involves the study of materials having dimensional range 1 to 100 nm. When the concept of nanotechnology is applied in the medical field, the resulting outcome is known as ‘Nanomedicine’. Nanomedicine generally includes nanoparticles, which are explored for various therapeutic applications. Various properties of nanoparticles like high reactivity, large surface area, and ultra small size make them highly efficient compared to conventional therapeutic agents. Methods: Present review discloses applications of various nanoparticulate systems in drug delivery and therapeutics. We searched nanoparticulate systems like liposomes, polymeric nanoparticles, lipidic nanoparticles, dendrimers, carbon nanotubes, and gold nanoparticles using search engines like PubMed and Google Scholar. Results: Results of a literature review regarding the use of nanoparticulate systems revealed their high preclinical efficacy, safety, and reduced toxicity compared to various traditional systems used for the delivery of various therapeutic agents. Implementation of targeting moieties like peptides, antibodies, or aptamers in nanoparticulate systems shows a synergistic effect in their efficacy. Conclusion: Nanoparticulate systems have shown significant effects on different areas of the medical field. However, clinical exploration of various nanoparticulate systems is still a challenge and this fact should be taken into consideration by pharmaceutical scientists. Despite this, nanomedicine is expected to have a tremendous effect on various areas of the medical field in the future.
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Milan, Andreea, Alexandra Mioc, Alexandra Prodea, Marius Mioc, Roxana Buzatu, Roxana Ghiulai, Roxana Racoviceanu, Florina Caruntu, and Codruţa Şoica. "The Optimized Delivery of Triterpenes by Liposomal Nanoformulations: Overcoming the Challenges." International Journal of Molecular Sciences 23, no. 3 (January 20, 2022): 1140. http://dx.doi.org/10.3390/ijms23031140.
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The last decade has witnessed a sustained increase in the research development of modern-day chemo-therapeutics, especially for those used for high mortality rate pathologies. However, the therapeutic landscape is continuously changing as a result of the currently existing toxic side effects induced by a substantial range of drug classes. One growing research direction driven to mitigate such inconveniences has converged towards the study of natural molecules for their promising therapeutic potential. Triterpenes are one such class of compounds, intensively investigated for their therapeutic versatility. Although the pharmacological effects reported for several representatives of this class has come as a well-deserved encouragement, the pharmacokinetic profile of these molecules has turned out to be an unwelcomed disappointment. Nevertheless, the light at the end of the tunnel arrived with the development of nanotechnology, more specifically, the use of liposomes as drug delivery systems. Liposomes are easily synthesizable phospholipid-based vesicles, with highly tunable surfaces, that have the ability to transport both hydrophilic and lipophilic structures ensuring superior drug bioavailability at the action site as well as an increased selectivity. This study aims to report the results related to the development of different types of liposomes, used as targeted vectors for the delivery of various triterpenes of high pharmacological interest.
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Szebeni, János, Lajos Baranyi, Sándor Sávay, Michael Bodó, János Milosevits, Carl R. Alving, and Rolf Bünger. "Complement activation-related cardiac anaphylaxis in pigs: role of C5a anaphylatoxin and adenosine in liposome-induced abnormalities in ECG and heart function." American Journal of Physiology-Heart and Circulatory Physiology 290, no. 3 (March 2006): H1050—H1058. http://dx.doi.org/10.1152/ajpheart.00622.2005.
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Cardiac anaphylaxis is a severe, life-threatening manifestation of acute hypersensitivity reactions to allergens and drugs. Earlier studies highlighted an amplifying effect of locally applied C5a on the process; however, the role of systemic complement (C) activation with C5a liberation in blood has not been explored to date. In the present study, we used the porcine liposome-induced cardiopulmonary distress model for 1) characterizing and quantifying peripheral C activation-related cardiac dysfunction; 2) exploring the role of C5a in cardiac abnormalities and therapeutic potential of C blockage by soluble C receptor type 1 (sCR1) and an anti-C5a antibody (GS1); and 3) elucidating the role of adenosine and adenosine receptors in paradoxical bradycardia, one of the symptoms observed in this model. Pigs were injected intravenously with different liposomes [Doxil and multilamellar vesicles (MLV)], zymosan, recombinant human (rhu) C5a, and adenosine, and the ensuing hemodynamic and cardiac changes (hypotension, tachy- or bradycardia, arrhythmias, ST-T changes, ventricular fibrillation, and arrest) were quantified by ranking on an arbitrary scale [cardiac abnormality score (CAS)]. There was significant correlation between CAS and C5a production by liposomes in vitro, and the liposome-induced cardiac abnormalities were partially or fully reproduced with zymosan, rhuC5a, adenosine, and the selective adenosine A1 receptor agonist cyclopentyl-adenosine. The use of C nonactivator liposomes or pretreatment of pigs with sCR1 or GS1 attenuated the abnormalities. The selective A1 blocker cyclopentyl-xanthine inhibited bradycardia without influencing hypotension, whereas the A2 blocker 4-(2-{7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino}ethyl)phenol (ZM-24135) had no such effect. These data suggest that 1) systemic C activation can underlie cardiac anaphylaxis, 2) C5a plays a causal role in the reaction, 3) adenosine action via A1 receptors may explain paradoxical bradycardia, and 4) inhibition of C5a formation or action or of A1-receptor function may alleviate the acute cardiotoxicity of liposomal drugs and other intravenous agents that activate C.
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Gilabert-Oriol, Roger, Gemma Ryan, Ada Leung, Natalie Firmino, Kevin Bennewith, and Marcel Bally. "Liposomal Formulations to Modulate the Tumour Microenvironment and Antitumour Immune Response." International Journal of Molecular Sciences 19, no. 10 (September 26, 2018): 2922. http://dx.doi.org/10.3390/ijms19102922.
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Tumours are complex systems of genetically diverse malignant cells that proliferate in the presence of a heterogeneous microenvironment consisting of host derived microvasculature, stromal, and immune cells. The components of the tumour microenvironment (TME) communicate with each other and with cancer cells, to regulate cellular processes that can inhibit, as well as enhance, tumour growth. Therapeutic strategies have been developed to modulate the TME and cancer-associated immune response. However, modulating compounds are often insoluble (aqueous solubility of less than 1 mg/mL) and have suboptimal pharmacokinetics that prevent therapeutically relevant drug concentrations from reaching the appropriate sites within the tumour. Nanomedicines and, in particular, liposomal formulations of relevant drug candidates, define clinically meaningful drug delivery systems that have the potential to ensure that the right drug candidate is delivered to the right area within tumours at the right time. Following encapsulation in liposomes, drug candidates often display extended plasma half-lives, higher plasma concentrations and may accumulate directly in the tumour tissue. Liposomes can normalise the tumour blood vessel structure and enhance the immunogenicity of tumour cell death; relatively unrecognised impacts associated with using liposomal formulations. This review describes liposomal formulations that affect components of the TME. A focus is placed on formulations which are approved for use in the clinic. The concept of tumour immunogenicity, and how liposomes may enhance radiation and chemotherapy-induced immunogenic cell death (ICD), is discussed. Liposomes are currently an indispensable tool in the treatment of cancer, and their contribution to cancer therapy may gain even further importance by incorporating modulators of the TME and the cancer-associated immune response.
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Adrien, Vladimir, Hugo Fumat, Cédric Tessier, Philippe Nuss, and David Tareste. "T202. THE EFFECT OF ANTIPSYCHOTIC DRUGS ON MEMBRANE FUSION: AN IN VITRO STUDY." Schizophrenia Bulletin 46, Supplement_1 (April 2020): S308—S309. http://dx.doi.org/10.1093/schbul/sbaa029.762.
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Abstract Background Common clinical use of antipsychotics (AP) drugs shows that their therapeutic mode of action still needs further clarification although it is admitted that the Dopamine receptor D2 (D2R) antagonism plays a significant role. For instance, clozapine (CLOZ) - which is known to be the most effective AP in treating schizophrenic symptoms - has strikingly the lowest D2R antagonism. Non direct receptor-related effects might thus be involved in the activity of AP at the synapse level. AP, as well as neurotransmitters, are mostly lipophilic and insert within membranes. This characteristic is of interest as a significant proportion of schizophrenic patients has specific and abnormal membrane lipid composition. This possible proxy of the disease biotype can participate in the disease’s physiopathology but also be critical for the effect of AP drugs. We hypothesize that AP insertion into lipid membranes also contribute to their therapeutic effect. AP-induced modifications of synaptic membranes biophysics are likely to influence neurotransmission. In this study, we focus on the effect of AP on membrane fusion, a crucial step for the exocytosis of neurotransmitters. Methods Liposomes modelling synaptic vesicles were reconstituted in saline buffer. Two standard ternary and quaternary lipid mixtures have been studied: phosphatidylcholine:phosphatidylethanolamine:phosphatidylserine (PC:PE:PS) [65:25:10] and the synaptic-like PC:PE:PS:sphingomyelin:cholesterol (PC:PE:PS:SM:CHOL) [25:25:10:10:30]. Some liposomes were protein-free and others were functionalized with Soluble N-ethylmaleimide-sensitive-factor Attachment protein Receptor (SNARE) proteins, which trigger in vivo the fusion of synaptic vesicles with the pre-synaptic plasma membrane. The liposome size was checked by Dynamic Light Scattering. Insertion of AP within the membrane was checked by second derivative spectroscopy. Fusion was measured by Fluorescence Resonance Energy Transfer in the absence or presence of CLOZ or chlorpromazine (CPZ) at various lipid:AP ratios (10:1 to 100000:1). Protein-free liposomes were fused with Polyethylene glycol (PEG) and SNARE liposomes through the action of cognate SNARE proteins residing in their membrane. Results Liposomes of the same lipid composition were of the same size, with no effect of the addition of AP drugs at various concentrations. Molar partition coefficient of AP drugs within the membrane of protein-free liposomes was approximately 70–85%. CPZ or CLOZ inhibited the fusion of PC:PE:PS liposomes by about 20–40%. When liposomes were synaptic-like (PC:PE:PS:SM:CHOL), the inhibition of fusion by AP drugs reached 50%. CLOZ also inhibited SNARE-mediated fusion of PC:PE:PS liposomes by about 30%. This effect on SNARE-mediated fusion was not observed with CPZ. Discussion Altogether, these results, despite preliminary, could help to understand partially a non direct receptor-related effect of antipsychotics. Indeed, these drugs also seem to modify membrane dynamics at the synapse level. This seems to be particularly the case of CLOZ on SNARE-mediated fusion and could explain its specific therapeutic efficiency.
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Moyá, Maria Luisa, Francisco José Ostos, Izamar Moreno, Diandra García, Paula Moreno-Gordillo, Ivan V. Rosado, Pilar López-Cornejo, José Antonio Lebrón, and Manuel López-López. "Metallo-Liposomes Derived from the [Ru(bpy)3]2+ Complex as Nanocarriers of Therapeutic Agents." Chemosensors 9, no. 5 (April 25, 2021): 90. http://dx.doi.org/10.3390/chemosensors9050090.
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The obtaining of nanocarriers of gene material and small drugs is still an interesting research line. Side-effects produced by the toxicity of several pharmaceutics, the high concentrations needed to get therapeutic effects, or their excessive use by patients have motivated the search for new nanostructures. For these reasons, cationic metallo-liposomes composed by phosphatidylcholine (PC), cholesterol (CHO) and RuC1C19 (a surfactant derived from the metallic complex [Ru(bpy)3]2+) were prepared and characterized by using diverse techniques (zeta potential, dynamic light scattering and electronic transmission microscopy –TEM-). Unimodal or bimodal populations of spherical aggregates with small sizes were obtained depending on the composition of the liposomes. The presence of cholesterol favored the formation of small aggregates. ct-DNA was condensed in the presence of the liposomes investigated. In-vitro assays demonstrated the ability of these nanoaggregates to internalize into different cell lines. A positive gene transfection into human bone osteosarcoma epithelial cells (U2OS) was also observed. The RuC1C19 surfactant was used as sensor to quantify the binding of DNA to the liposomes. Doxorubicin was encapsulated into the metallo-liposomes, demonstrating their ability to be also used as nanocarriers of drugs. A relationship between then encapsulation percentage of the antibiotic and the composition of the aggregates has been established.
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Sawant, Ganesh Shankar, Kiran Vilas Sutar, and Akhil S. Kanekar. "Liposome: A Novel Drug Delivery System." International Journal of Research and Review 8, no. 4 (April 21, 2021): 252–68. http://dx.doi.org/10.52403/ijrr.20210433.
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Liposome is a spherical sac phospholipid molecule. It encloses a water droplet especially as form artificially to carry drug into tissue membrane. It is spherical sac vesicle it consists at least one lipid bilayer. Liposomes are mainly development for drug delivery size and size distribution. The process of sonication (extrusion) is required to obtain small size and narrow size distribution of liposome. The main significant role in formulating of potent drug, improve therapeutic effect. Liposome formulation is mainly design in increasing accumulation at the target site, and then resulting effect is targeted to reduce toxicity. There is various method for liposome formulation depending upon lipid drug interaction liposome disposition mechanism- parameters particle size, charge and surface hydration. Liposome is a nanoparticle (size-100nm). Nanoscale drug delivery system using liposome as well as nanoparticle. This technology is for "Rational delivery of chemotherapeutic" drug treatment of cancer. Liposome is use as to study the cell membrane and cell organelles. The advantages of liposome formation using microfluidic approach for bulk-mixing approaches are discussed. Keywords: liposome, lipid bilayer, sonication, nanoparticles, particle size, toxicity.
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Jose, Gils, Yu-Jen Lu, Jung-Tung Hung, Alice L. Yu, and Jyh-Ping Chen. "Co-Delivery of CPT-11 and Panobinostat with Anti-GD2 Antibody Conjugated Immunoliposomes for Targeted Combination Chemotherapy." Cancers 12, no. 11 (October 31, 2020): 3211. http://dx.doi.org/10.3390/cancers12113211.
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The consistent expression of disialoganglioside GD2 in neuroblastoma tumor cells and its restricted expression in normal tissues open the possibility to use it for molecularly targeted neuroblastoma therapy. On the other hand, immunoliposomes combining antibody-mediated tumor recognition with liposomal delivery of chemotherapeutics have been proved to enhance therapeutic efficacy in brain tumors. Therefore, we develop immunoliposomes (ImmuLipCP) conjugated with anti-GD2 antibody, for targeted co-delivery of CPT-11 and panobinostat in this study. U87MG human glioma cell line and its drug resistant variant (U87DR), which were confirmed to be associated with low and high expression of cell surface GD2, were employed to compare the targeting efficacy. From in vitro cytotoxicity assay, CPT-11 showed synergism drug interaction with panobinostat to support co-delivery of both drugs with ImmuLipCP for targeted synergistic combination chemotherapy. The molecular targeting mechanism was elucidated from intracellular uptake efficacy by confocal microscopy and flow cytometry analysis, where 6-fold increase in liposome and 1.8-fold increase in drug uptake efficiency was found using targeted liposomes. This enhanced intracellular trafficking for drug delivery endows ImmuLipCP with pronounced cytotoxicity toward U87DR cells in vitro, with 1.6-fold increase of apoptosis rate. Using xenograft nude mice model with subcutaneously implanted U87DR cells, we observe similar biodistribution profile but 5.1 times higher accumulation rate of ImmuLip from in vivo imaging system (IVIS) observation of Cy5.5-labelled liposomes. Taking advantage of this highly efficient GD-2 targeting, ImmuLipCP was demonstrated to be an effective cancer treatment modality to significantly enhance the anti-cancer therapeutic efficacy in U87DR tumors, shown from the significant reduced tumor size in and prolonged survival time of experiment animals as well as diminished expression of cell proliferation and enhanced expression of apoptosis marker proteins in tumor section.
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Viet Nguyen, Khan, Ivo Laidmäe, Karin Kogermann, Andres Lust, Andres Meos, Duc Viet Ho, Ain Raal, Jyrki Heinämäki, and Hoai Thi Nguyen. "Preformulation Study of Electrospun Haemanthamine-Loaded Amphiphilic Nanofibers Intended for a Solid Template for Self-Assembled Liposomes." Pharmaceutics 11, no. 10 (September 29, 2019): 499. http://dx.doi.org/10.3390/pharmaceutics11100499.
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Haemanthamine (HAE) has been proven as a potential anticancer agent. However, the therapeutic use of this plant-origin alkaloid to date is limited due to the chemical instability and poorly water-soluble characteristics of the agent. To overcome these challenges, we developed novel amphiphilic electrospun nanofibers (NFs) loaded with HAE, phosphatidylcholine (PC) and polyvinylpyrrolidone (PVP), and intended for a stabilizing platform (template) of self-assembled liposomes of the active agent. The NFs were fabricated with a solvent-based electrospinning method. The chemical structure of HAE and the geometric properties, molecular interactions and physical solid-state properties of the NFs were investigated using nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), photon correlation spectroscopy (PCS), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC), respectively. An in-house dialysis-based dissolution method was used to investigate the drug release in vitro. The HAE-loaded fibers showed a nanoscale size ranging from 197 nm to 534 nm. The liposomes with a diameter between 63 nm and 401 nm were spontaneously formed as the NFs were exposed to water. HAE dispersed inside liposomes showed a tri-modal dissolution behavior. In conclusion, the present amphiphilic NFs loaded with HAE are an alternative approach for the formulation of a liposomal drug delivery system and stabilization of the liposomes of the present alkaloid.
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Tan, Kuan Boone, Leong Uung Ling, and Gigi Ngar Chee Chiu. "In Vitro Efficacy of a Novel Liposomal Formulation of a Protein Kinase C Inhibitor In the Treatment of Acute Myeloid Leukemia." Blood 116, no. 21 (November 19, 2010): 3282. http://dx.doi.org/10.1182/blood.v116.21.3282.3282.
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Abstract Abstract 3282 The prognosis of patients with acute myeloid leukemia (AML) remains poor, despite the use of the first-line, anthracycline- and cytarabine-based induction chemotherapy aiming to induce complete remission in patients. Given the recent findings that intensive chemotherapy may not benefit older leukemia patients who are not candidates for stem cell transplantation (Kantarjian, H. et al, Blood, 2010; DOI: 10.1182/blood-2010-03-276485) and that the monoclonal antibody-based cytotoxic agent, gemtuzumab ozogamicin, has been voluntarily withdrawn from the market, there is a pressing need to find effective treatment for recurrent AML patients who are >60 years. Safingol [(2S, 3S)-2-amino-1,3-octadecanediol] is a potential anti-cancer bioactive lipid that induces apoptosis through PKC inhibition in leukemia cells and other cancer types. Owing to its poor solubility, safingol is administered as an oil-based emulsion; however, this formulation suffers from severe hemolysis as the dose-limiting toxicity in pre-clinical models, and its toxicity profile is yet to be determined from an ongoing Phase I clinical trial for advanced solid tumors. Liposome is a commonly used drug delivery system to solubilize hydrophobic drugs. It is anticipated that liposome encapsulation of safingol would yield a viable injectable drug product without the need of toxic vehicle such as ethanol or Cremophor-EL, and would substantially reduce the hemolytic toxicity of safingol. In this study, our intention is to develop a suitable liposome formulation of safingol and to test its therapeutic efficacy using human AML cell lines and primary patient samples. Safingol could be formulated into stable liposomes using distearyolphosphatidylcholine and cholesterol with encapsulation efficiency of ∼100%. Safingol was released from the liposomes with a sustained release profile, mainly by a diffusion-controlled mechanism. The extent of hemolysis of 0.5 mM safingol could be significantly reduced from 76% to 14% through liposome encapsulation, as determined by an in vitro hemolysis assay. The cytotoxicity of liposomal safingol was tested with MTT assay on various AML cell lines representing different subtypes, including KG-1 (M1), HL-60 (M2), NB4 (M3), U937 (M5), MV4-11 (M5) and HEL (M6), as well as K562, a cell line of blast crisis of chronic myelogenous leukemia (BC-CML). All cell lines tested responded well to the treatment of liposomal safingol, with IC50 values ranging from 1.5–14 μM. Among the various AML subtypes, NB4 was found to be the most sensitive cell line with the lowest IC50 value of 1.5±0.2 μM. Importantly, liposome encapsulation of safingol did not compromise the ability of the drug to induce apoptosis as compared to the free drug, which was mediated possibly through a mechanism dependent on the generation of reactive oxygen species and caspase activation. Liposomal safingol was further tested in 10 leukemic patient samples, and the formulation was able to induce complete loss of viability of the primary cell samples at 20 μM after 72 h of treatment. Taken together, our results demonstrated the therapeutic potential of liposomal safingol for the treatment of various AML subtypes. Further evaluation of the pharmacokinetics and the efficacy of the formulation in animal models is warranted. Disclosures: No relevant conflicts of interest to declare.
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Rogers, M. S., R. P. Patel, B. J. Reeder, P. Sarti, M. T. Wilson, and A. I. Alayash. "Pro-oxidant effects of cross-linked haemoglobins explored using liposome and cytochrome c oxidase vesicle model membranes." Biochemical Journal 310, no. 3 (September 15, 1995): 827–33. http://dx.doi.org/10.1042/bj3100827.
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The therapeutic use of cell-free haemoglobin as a blood substitute has been hampered by toxicological effects. A model asolectin (phosphatidylcholine/phosphatidylethanolamine) liposome system was utilized to study the pro-oxidant efficiency of several chemically modified haemoglobins on biological membranes. Lipid peroxidation, resulting from the interactions between haemoglobin and liposomes, was measured by conjugated diene formation and the maximal rates of oxygen uptake. Spectral changes gave insight into the occurrence of the ferryl iron species. The residual reactivity of oxidatively damaged haemoglobins with ligands during incubation with liposomes was assessed from rapid kinetic carbon monoxide-binding experiments. Liposomes in which cytochrome c oxidase was embedded show both haemoglobin and the enzyme to be oxidatively damaged during incubation. The functional state of cytochrome c oxidase was monitored in the presence and absence of a free radical scavenger. Once in contact, both unmodified and modified haemoglobins triggered and maintained severe radical-mediated membrane damage. Differences in the pro-oxidant activities among haemoglobins may be explained by either the differential population of their ferryl intermediates or disparate dimerization and transfer of haem into the membrane with subsequent haem degradation. This study may contribute to a better understanding of the molecular determinants of haemoglobin interactions with a variety of biological membranes.
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Peeters, P. A. M., Caroline W. E. M. Huiskamp, W. M. C. Eling, and D. J. A. Crommelin. "Chloroquine containing liposomes in the chemotherapy of murine malaria." Parasitology 98, no. 3 (June 1989): 381–86. http://dx.doi.org/10.1017/s003118200006145x.
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SUMMARYIn this study, the advantage of the use of chloroquine (CQ) containing liposomes (lipCQ) over free CQ in the chemotherapy of murine malaria (Plasmodium berghei) was demonstrated. The maximum permissible dose per intraperitoneal injection was 0·8 and 10 mg for CQ and lipCQ, respectively. An increase in therapeutic and prophylactic efficacy of lipCQ in comparison with free CQ at a 0·8 mg CQ dose level was found. It was possible to obtain 100% efficacy (injection at day 5 after infection; parasitaemia 4–8%) with one single intraperitoneal injection of 6 mg lipCQ. Moreover, the ability to increase the doses of CQ per injection after liposome encapsulation allowed successful treatment of infections with CQ-resistant Plasmodium berghei which could not be cured by a 7-day course with the maximum tolerable dose of free CQ of 0·8 mg/mouse/day.
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Ануфриев, Илья Евгеньевич, Екатерина Николаевна Муратова, Дмитрий Владимирович Королев, Галина Анатольевна Шульмейтер, Ришат Галеевич Валеев, and Вячеслав Алексеевич Мошников. "DEVELOPMENT OF A MANUAL EXTRUDER FOR LIPOSOME HOMOGENIZATION." Physical and Chemical Aspects of the Study of Clusters, Nanostructures and Nanomaterials, no. 14 (December 15, 2022): 8–16. http://dx.doi.org/10.26456/pcascnn/2022.14.008.
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Лекарственные препараты с использованием липосом вызывают большой интерес в фармацевтике. Они повышают терапевтический индекс препарата за счет заключения лекарственного вещества внутрь биосовместимой липидной оболочки, которая выпускает раствор только в необходимой области. Такие лекарства уже показали свою эффективность при лечении заболеваний, связанных с онкологией, дерматологией неврологией, хирургией и др. Для использования липосом в этих целях, необходимо чтобы их размер был в интервале от 50 до 200 нм. Существует несколько способов создать везикулы такого размера, но в основном используют либо воздействие ультразвука на раствор липосом, либо экструзию. Метод экструзии является методом, позволяющим получить наиболее гомогенный раствор из липосомальных частиц. Для проведения экструзии, требуется специальный прибор -экструдер. Он представляет собой систему, пропускающую под давлением липосомальный раствор через фильтр с определенным размером пор. В данной работе рассмотрен процесс экструзии липосом, виды липосомальных экструдеров и оценены их плюсы и минусы, так же была разработана модель ручного экструдера, способного гомогенизировать до 20 мл раствора. Были рассмотрены и использованы разные материалы для конструкции данного прибора. Проверка экструдера показала его работоспособность и показала преимущества использования экструзии по сравнению с методом воздействия ультразвука. Medications using liposomes are of great interest in pharmaceuticals. They increase the therapeutic index of the drug by enclosing the medicinal substance inside a biocompatible lipid envelope, which releases the solution only in the required area. Such drugs have already shown their effectiveness in the treatment of diseases related to oncology, dermatology, neurology, surgery, etc. To use liposomes for these purposes, it is necessary that their size be in the range from 50 to 200 nm. There are several ways to create vesicles of this size, but mostly they use either ultrasound exposure to a liposome solution or extrusion. The extrusion method is a method that allows to obtain the most homogeneous solution from liposomal particles. For extrusion, a special device - an extruder is required. It is a system that passes a liposomal solution under pressure through a filter with a certain pore size. In this paper, the process of liposome extrusion, types of liposomal extruders are considered and their pros and cons are evaluated, a model of a manual extruder capable of homogenizing up to 20 ml of solution was also developed. Different materials were considered and used for the construction of this device. The inspection of the extruder showed its operability and showed the advantages of using extrusion compared to the ultrasound exposure method.
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Brown, Sarah, and David R. Khan. "The Treatment of Breast Cancer Using Liposome Technology." Journal of Drug Delivery 2012 (February 21, 2012): 1–6. http://dx.doi.org/10.1155/2012/212965.
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Liposome-based chemotherapeutics used in the treatment of breast cancer can in principle enhance the therapeutic index of otherwise unencapsulated anticancer drugs. This is partially attributed to the fact that encapsulation of cytotoxic agents within liposomes allows for increased concentrations of the drug to be delivered to the tumor site. In addition, the presence of the phospholipid bilayer prevents the encapsulated active form of the drug from being broken down in the body prior to reaching tumor tissue and also serves to minimize exposure of the drug to healthy sensitive tissue. While clinically approved liposome-based chemotherapeutics such as Doxil have proven to be quite effective in the treatment of breast cancer, significant challenges remain involving poor drug transfer between the liposome and cancerous cells. In this review, we discuss the recent advancements made in the development of liposome-based chemotherapeutics with respect to improved drug transfer for use in breast cancer therapy.
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Kolašinac, Rejhana, Dirk Bier, Laura Schmitt, Andriy Yabluchanskiy, Bernd Neumaier, Rudolf Merkel, and Agnes Csiszár. "Delivery of the Radionuclide 131I Using Cationic Fusogenic Liposomes as Nanocarriers." International Journal of Molecular Sciences 22, no. 1 (January 5, 2021): 457. http://dx.doi.org/10.3390/ijms22010457.
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Liposomes are highly biocompatible and versatile drug carriers with an increasing number of applications in the field of nuclear medicine and diagnostics. So far, only negatively charged liposomes with intercalated radiometals, e.g., 64Cu, 99mTc, have been reported. However, the process of cellular uptake of liposomes by endocytosis is rather slow. Cellular uptake can be accelerated by recently developed cationic liposomes, which exhibit extraordinarily high membrane fusion ability. The aim of the present study was the development of the formulation and the characterization of such cationic fusogenic liposomes with intercalated radioactive [131I]I− for potential use in therapeutic applications. The epithelial human breast cancer cell line MDA-MB-231 was used as a model for invasive cancer cells and cellular uptake of [131I]I− was monitored in vitro. Delivery efficiencies of cationic and neutral liposomes were compared with uptake of free iodide. The best cargo delivery efficiency (~10%) was achieved using cationic fusogenic liposomes due to their special delivery pathway of membrane fusion. Additionally, human blood cells were also incubated with cationic control liposomes and free [131I]I−. In these cases, iodide delivery efficiencies remained below 3%.
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Giraldo, Kevin A., Juan Sebastian Bermudez, Samuel Torres, Luis H. Reyes, Johann F. Osma, and Juan C. Cruz. "Modeling and Simulation of Multiphase Flow for Nanoparticle Translocation." Materials Proceedings 4, no. 1 (November 15, 2020): 71. http://dx.doi.org/10.3390/iocn2020-07796.
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The delivery of bioactive compounds is often improved by their encapsulation within systems based on different materials, such as polymers and phospholipids. In this regard, one of the most attractive vehicles are liposomes, which can be produced by the self-assembly of phospholipids in aqueous buffered systems. Encapsulation of therapeutic magnetite nanoparticles (MNPs) within liposomes can be accomplished by direct translocation of their lipid bilayer by surface conjugation of potent translocating peptides (and proteins) such as Buforin-II and OmpA. Here, we put forward the notion that to achieve reproducibility and optimize this process, it is possible to develop microfluidic systems that use flow-focusing methods to manipulate the interaction of suspended MNPs (ferrofluids) with the liposomes. With that in mind, we have developed an in silico approach to predict the performance of microfluidic devices specifically designed for the encapsulation process. This was done by running multiphysics simulations in COMSOL to evaluate the macroscopic flow of liposomes and suspended MNPs via a multiphase mixture model. Moreover, we estimated the corresponding interaction using a chemical reaction model based on embedding the Michaelis–Menten equation within the diluted species module’s transport. In this case, the enzymes-substrate interaction was considered similar to that of the MNPs-liposome. As a result, we were able to approach saturation kinetics that resemble that obtained experimentally for the uptake of functionalized MNPs. Future work will be directed towards refining the model by considering more details on the possible stages during the interaction of the involved intermediates.
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Peñate Medina, Tuula, Mirko Gerle, Jana Humbert, Hanwen Chu, Anna-Lena Köpnick, Reinhard Barkmann, Vasil M. Garamus, et al. "Lipid-Iron Nanoparticle with a Cell Stress Release Mechanism Combined with a Local Alternating Magnetic Field Enables Site-Activated Drug Release." Cancers 12, no. 12 (December 14, 2020): 3767. http://dx.doi.org/10.3390/cancers12123767.
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Most available cancer chemotherapies are based on systemically administered small organic molecules, and only a tiny fraction of the drug reaches the disease site. The approach causes significant side effects and limits the outcome of the therapy. Targeted drug delivery provides an alternative to improve the situation. However, due to the poor release characteristics of the delivery systems, limitations remain. This report presents a new approach to address the challenges using two fundamentally different mechanisms to trigger the release from the liposomal carrier. We use an endogenous disease marker, an enzyme, combined with an externally applied magnetic field, to open the delivery system at the correct time only in the disease site. This site-activated release system is a novel two-switch nanomachine that can be regulated by a cell stress-induced enzyme at the cellular level and be remotely controlled using an applied magnetic field. We tested the concept using sphingomyelin-containing liposomes encapsulated with indocyanine green, fluorescent marker, or the anticancer drug cisplatin. We engineered the liposomes by adding paramagnetic beads to act as a receiver of outside magnetic energy. The developed multifunctional liposomes were characterized in vitro in leakage studies and cell internalization studies. The release system was further studied in vivo in imaging and therapy trials using a squamous cell carcinoma tumor in the mouse as a disease model. In vitro studies showed an increased release of loaded material when stress-related enzyme and magnetic field was applied to the carrier liposomes. The theranostic liposomes were found in tumors, and the improved therapeutic effect was shown in the survival studies.
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Lee, Chia-Ying, Tsuimin Tsai, Po-Chun Peng, and Chin-Tin Chen. "Fabrication of Doxorubicin-Loaded Lipid-Based Nanocarriers by Microfluidic Rapid Mixing." Biomedicines 10, no. 6 (May 27, 2022): 1259. http://dx.doi.org/10.3390/biomedicines10061259.
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Doxorubicin (Dox) is a widely known chemotherapeutic drug that has been encapsulated into liposomes for clinical use, such as Doxil® and Myocet®. Both of these are prepared via remote loading methods, which require multistep procedures. Additionally, their antitumor efficacy is hindered due to the poor drug release from PEGylated liposomes in the tumor microenvironment. In this study, we aimed to develop doxorubicin-loaded lipid-based nanocarriers (LNC-Dox) based on electrostatic interaction using microfluidic technology. The resulting LNC-Dox showed high loading capacity, with a drug-to-lipid ratio (D/L ratio) greater than 0.2, and high efficacy of drug release in an acidic environment. Different lipid compositions were selected based on critical packing parameters and further studied to outline their effects on the physicochemical characteristics of LNC-Dox. Design of experiments was implemented for formulation optimization. The optimized LNC-Dox showed preferred release in acidic environments and better therapeutic efficacy compared to PEGylated liposomal Dox in vivo. Thus, this study provides a feasible approach to efficiently encapsulate doxorubicin into lipid-based nanocarriers fabricated by microfluidic rapid mixing.