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1
Marqués-Gallego, Patricia, and Anton I. P. M. de Kroon. "Ligation Strategies for Targeting Liposomal Nanocarriers." BioMed Research International 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/129458.
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Liposomes have been exploited for pharmaceutical purposes, including diagnostic imaging and drug and gene delivery. The versatility of liposomes as drug carriers has been demonstrated by a variety of clinically approved formulations. Since liposomes were first reported, research of liposomal formulations has progressed to produce improved delivery systems. One example of this progress is stealth liposomes, so called because they are equipped with a PEGylated coating of the liposome bilayer, leading to prolonged blood circulation and improved biodistribution of the liposomal carrier. A growing research area focuses on the preparation of liposomes with the ability of targeting specific tissues. Several strategies to prepare liposomes with active targeting ligands have been developed over the last decades. Herein, several strategies for the functionalization of liposomes are concisely summarized, with emphasis on recently developed technologies for the covalent conjugation of targeting ligands to liposomes.
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Nikolova, Maria P., Enamala Manoj Kumar, and Murthy S. Chavali. "Updates on Responsive Drug Delivery Based on Liposome Vehicles for Cancer Treatment." Pharmaceutics 14, no. 10 (October 15, 2022): 2195. http://dx.doi.org/10.3390/pharmaceutics14102195.
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Liposomes are well-known nanoparticles with a non-toxic nature and the ability to incorporate both hydrophilic and hydrophobic drugs simultaneously. As modern drug delivery formulations are produced by emerging technologies, numerous advantages of liposomal drug delivery systems over conventional liposomes or free drug treatment of cancer have been reported. Recently, liposome nanocarriers have exhibited high drug loading capacity, drug protection, improved bioavailability, enhanced intercellular delivery, and better therapeutic effect because of resounding success in targeting delivery. The site targeting of smart responsive liposomes, achieved through changes in their physicochemical and morphological properties, allows for the controlled release of active compounds under certain endogenous or exogenous stimuli. In that way, the multifunctional and stimuli-responsive nanocarriers for the drug delivery of cancer therapeutics enhance the efficacy of treatment prevention and fighting over metastases, while limiting the systemic side effects on healthy tissues and organs. Since liposomes constitute promising nanocarriers for site-targeted and controlled anticancer drug release, this review focuses on the recent progress of smart liposome achievements for anticancer drug delivery applications.
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Yan, Wei, Sharon SY Leung, and Kenneth KW To. "Updates on the use of liposomes for active tumor targeting in cancer therapy." Nanomedicine 15, no. 3 (February 2020): 303–18. http://dx.doi.org/10.2217/nnm-2019-0308.
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In the development of cancer chemotherapy, besides the discovery of new anticancer drugs, a variety of nanocarrier systems for the delivery of previously developed and new chemotherapeutic drugs have currently been explored. Liposome is one of the most studied nanocarrier systems because of its biodegradability, simple preparation method, high efficacy and low toxicity. To make the best use of this vehicle, a number of multifunctionalized liposomal formulations have been investigated. The objective of this review is to summarize the current development of novel active targeting liposomal formulations, and to give insight into the challenges and future direction of the field. The recent studies in active targeting liposomes suggest the great potential of precise targeted anticancer drug delivery in cancer therapeutics.
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Andreana, Ilaria, Valeria Bincoletto, Maela Manzoli, Francesca Rodà, Vita Giarraputo, Paola Milla, Silvia Arpicco, and Barbara Stella. "Freeze Drying of Polymer Nanoparticles and Liposomes Exploiting Different Saccharide-Based Approaches." Materials 16, no. 3 (January 31, 2023): 1212. http://dx.doi.org/10.3390/ma16031212.
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Biodegradable nanocarriers represent promising tools for controlled drug delivery. However, one major drawback related to their use is the long-term stability, which is largely influenced by the presence of water in the formulations, so to solve this problem, freeze-drying with cryoprotectants has been proposed. In the present study, the influence of the freeze-drying procedure on the storage stability of poly(lactide-co-glycolide) (PLGA) nanoparticles and liposomes was evaluated. In particular, conventional cryoprotectants were added to PLGA nanoparticle and liposome formulations in various conditions. Additionally, hyaluronic acid (HA), known for its ability to target the CD44 receptor, was assessed as a cryoprotective excipient: it was added to the nanocarriers as either a free molecule or conjugated to a phospholipid to increase the interaction with the polymer or lipid matrix while exposing HA on the nanocarrier surface. The formulations were resuspended and characterized for size, polydispersity index, zeta potential and morphology. It was demonstrated that only the highest percentages of cryoprotectants allowed the resuspension of stable nanocarriers. Moreover, unlike free HA, HA-phospholipid conjugates were able to maintain the particle mean size after the reconstitution of lyophilized nanoparticles and liposomes. This study paves the way for the use of HA-phospholipids to achieve, at the same time, nanocarrier cryoprotection and active targeting.
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Yue, Xiuli, and Zhifei Dai. "Liposomal Nanotechnology for Cancer Theranostics." Current Medicinal Chemistry 25, no. 12 (April 19, 2018): 1397–408. http://dx.doi.org/10.2174/0929867324666170306105350.
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Liposomes are a type of biomimetic nanoparticles generated from self-assembling concentric lipid bilayer enclosing an aqueous core domain. They have been attractive nanocarriers for the delivery of many drugs (e.g. radiopharmaceuticals, chemotherapeutic agents, porphyrin) and diagnostic agents (e.g. fluorescent dyes, quantum dots, Gadolinium complex and Fe3O4) by encapsulating (or adsorbing) hydrophilic one inside the liposomal aqueous core domain (or on the bilayer membrane surface), and by entrapping hydrophobic one within the liposomal bilayer. Additionally, the liposome surface can be easily conjugated with targeting molecules. Liposomes may accumulate in cancerous tissues not only passively via enhanced permeability and retention (EPR) effect, but also actively by targeting cancer cell or angiogenic marker specifically. The multimodality imaging functionalization of liposomal therapeutic agents makes them highly attractive for individualized monitoring of the in vivo cancer targeting and pharmacokinetics of liposomes loading therapeutic drugs, and predicting therapeutic efficacy in combination with the helpful information from each imaging technique. The present review article will highlight some main advances of cancer theranostic liposomes with a view to activate further research in the nanomedicine community.
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Tansi, Felista L., Ronny Rüger, Ansgar M. Kollmeier, Markus Rabenhold, Frank Steiniger, Roland E. Kontermann, Ulf K. Teichgräber, Alfred Fahr, and Ingrid Hilger. "Targeting the Tumor Microenvironment with Fluorescence-Activatable Bispecific Endoglin/Fibroblast Activation Protein Targeting Liposomes." Pharmaceutics 12, no. 4 (April 17, 2020): 370. http://dx.doi.org/10.3390/pharmaceutics12040370.
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Liposomes are biocompatible nanocarriers with promising features for targeted delivery of contrast agents and drugs into the tumor microenvironment, for imaging and therapy purposes. Liposome-based simultaneous targeting of tumor associated fibroblast and the vasculature is promising, but the heterogeneity of tumors entails a thorough validation of suitable markers for targeted delivery. Thus, we elucidated the potential of bispecific liposomes targeting the fibroblast activation protein (FAP) on tumor stromal fibroblasts, together with endoglin which is overexpressed on tumor neovascular cells and some neoplastic cells. Fluorescence-quenched liposomes were prepared by hydrating a lipid film with a high concentration of the self-quenching near-infrared fluorescent dye, DY-676-COOH, to enable fluorescence detection exclusively upon liposomal degradation and subsequent activation. A non-quenched green fluorescent phospholipid was embedded in the liposomal surface to fluorescence-track intact liposomes. FAP- and murine endoglin-specific single chain antibody fragments were coupled to the liposomal surface, and the liposomal potentials validated in tumor cells and mice models. The bispecific liposomes revealed strong fluorescence quenching, activatability, and selectivity for target cells and delivered the encapsulated dye selectively into tumor vessels and tumor associated fibroblasts in xenografted mice models and enabled their fluorescence imaging. Furthermore, detection of swollen lymph nodes during intra-operative simulations was possible. Thus, the bispecific liposomes have potentials for targeted delivery into the tumor microenvironment and for image-guided surgery.
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Fathalla, Dina, Eman M. K. Youssef, and Ghareb M. Soliman. "Liposomal and Ethosomal Gels for the Topical Delivery of Anthralin: Preparation, Comparative Evaluation and Clinical Assessment in Psoriatic Patients." Pharmaceutics 12, no. 5 (May 11, 2020): 446. http://dx.doi.org/10.3390/pharmaceutics12050446.
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To enhance anthralin efficacy against psoriasis and reduce its notorious side effects, it was loaded into various liposomal and ethosomal preparations. The nanocarriers were characterized for drug encapsulation efficiency, size, morphology and compatibility between various components. Optimum formulations were dispersed in various gel bases and drug release kinetics were studied. Clinical efficacy and safety of liposomal and ethosomal Pluronic®F-127 gels were evaluated in patients having psoriasis (clinicaltrials.gov identifier is NCT03348462). Safety was assessed by recording various adverse events. Drug encapsulation efficiency ≥97.2% and ≥77% were obtained for liposomes and ethosomes, respectively. Particle sizes of 116 to 199 nm and 146 to 381 nm were observed for liposomes and ethosomes, respectively. Fourier-Transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) studies confirmed the absence of interaction between anthralin and various nanocarrier components. Tested gel bases showed excellent ability to sustain drug release. At baseline, the patients had a median Psoriasis Area and Severity Index (PASI) of 3.4 for liposomes and 3.6 for ethosomes without significant difference. After treatment, mean PASI change was −68.66% and −81.84% for liposomes and ethosomes, respectively with a significant difference in favor of ethosomes. No adverse effects were detected in both groups. Anthralin ethosomes could be considered as a potential treatment of psoriasis.
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Al-Mahmood, Sumayah. "Targeting Breast Cancer Stem Cells (BCSCs) with Liposomal Formulations." Clinical Cancer Drugs 6, no. 1 (September 27, 2019): 3–7. http://dx.doi.org/10.2174/2212697x06666190318150757.
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Breast cancer stem cells (BCSCs) are a small proportion of cells that may be responsible for improving the resistance of cancer cells to the treatment and metastasis of breast cancer (MBC). Nanovehicles such as liposomes are extensively explored for diagnosis, treatment, and imaging of cancer. Targeted therapy with nanoparticles can be used to overcome the chemoresistance problem of cancer stem cells. Liposomes are lipid bilayer nanocarriers that have the ability to inhibit Pglycoprotein to overcome multidrug resistance that makes liposome ideal choice for using in BCSCs therapy. The main objective of this review is to describe novel liposomal formulations that are used in targeting BCSCs, which help in improving breast cancer treatment.
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Perminaite, Kristina, Anna Maria Fadda, Chiara Sinico, and Kristina Ramanauskiene. "Formulation of Liposomes Containing Royal Jelly and Their Quality Assessment." Journal of Nanoscience and Nanotechnology 21, no. 5 (May 1, 2021): 2841–46. http://dx.doi.org/10.1166/jnn.2021.19053.
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Royal jelly, a gelatinuous consistency bee product produced and secreted by the hypopharyngeal and mandibular glands of worker honeybees, is beneficial in the treatment of dermatological conditions, likely through its content of the fatty acid 10-hydroxy-2-decenoic acid (10-HDA). However, 10-HAD poorly penetrates into skin. Thus, in this work, we produced royal jelly incorporated liposomes with the aim of increasing skin penetration of 10-HDA. Lipid nanocarriers were prepared by the thin lipid-film hydration method. Size and polydispersity index of the nanocarrier particles, and their stability over 30 days were measured. The effects of royal jelly and 10-HDA liposomal formulations on the viability of immortalized human keratinocyte cells were tested with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The skin penetration of 10-HDA from liposomal formulations and royal jelly solution was studied in vitro with Franz type vertical diffusion cells using porcine skin as limiting membrane. As result, small liposomes were achieved, and the efficacy of the obtained nanoformulations was examined by means of in vitro cell assays with a HaCaT immortalized human keratinocyte cell culture line. Finally, the skin penetration experiments showed that liposomal incorporation greatly increased 10-HDA penetration into skin layers.
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Pandya, Tosha, Kaushika Kaushika Patel, Rudree Pathak, and Shreeraj Shah. "Liposomal Formulations In Cancer Therapy: Passive Versus Active Targeting." Asian Journal of Pharmaceutical Research and Development 7, no. 2 (April 14, 2019): 35–38. http://dx.doi.org/10.22270/ajprd.v7i2.489.
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In Cancer therapy, Nano drug delivery system comprising of Liposomes, are the most successful mode of treatment in present scenario which also has real time clinical application. Recently it is found that the closed bilayer phospholipid vesicles have many technical advantages over the initially used liposomal formulations. The delivery of therapeutics encapsulated in liposomes changes the biological distribution profile and improves the drug therapeutic indices of various drugs. This review article throws light onto many clinical liposomal drug delivery products. The liposome Nano drug delivery by the active and passive targeting is a boon as it can reduce the off-targeting effects. The current development is more focused on the diagnostic and clinical applications. Receptor targeted delivery systems are extensively explored for active targeting. However, these delivery systems are rarely seen in the clinical application because of conjugation chemistry and other implicit hurdles to develop this system.The development of nanocarriers in the cancer treatment have enormous potential in the medical field. Moreover, Immuno liposomes have been used in cancer treatment as attractive drug targeting vehicles. On the other hand, there are many other liposomal drug delivery systems having passive targeting mechanism for cancer treatment which are widely used due to enhanced retention and permeability of formulation. This review majorly focuses on the current challenges encountered in development of liposomal Nano drug delivery systems and its effective development for cancer treatment.
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WONG, MAN-YI, and GIGI N. C. CHIU. "DEVELOPMENT AND CHARACTERIZATION OF A NANOCARRIER FOR QUERCETIN." International Journal of Nanoscience 08, no. 01n02 (February 2009): 175–79. http://dx.doi.org/10.1142/s0219581x09005979.
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Quercetin is a naturally occurring cytotoxic compound where clinical use has been limited by its low water solubility. Therefore, liposomes were explored for solubilizing quercetin. Liposomes composed of DPPC (1,2 dipalmitoyl-sn-glycerol-3-phosphocholine)/DSPE-PEG2000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)2000])/quercetin (90:5:5 mole ratio) incorporated quercetin efficiently at 100.9 ± 4.6% and increased quercetin concentration in water 11.2-fold. Stability studies at storage temperature of 4°C showed that the liposomes were stable for up to 16 weeks, without any significant changes in diameters. Liposomal quercetin showed a delayed release profile and reduced quercetin degradation. In vitro cytotoxicity tests also showed that the ED50 of liposomal quercetin was 17.6 times lower than free quercetin in MDA-MB-231 breast cancer cells. In conclusion, the DPPC/DSPE-PEG-based liposomes were stable and were capable of solubilizing quercetin, preventing quercetin degradation, and increasing quercetin in vitro cytotoxicity. Hence, liposomes are a suitable nanocarrier for quercetin.
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Manzano, Miguel, Alberto Gabizón, and María Vallet-Regí. "Characterization of a Mesoporous Silica Nanoparticle Formulation Loaded with Mitomycin C Lipidic Prodrug (MLP) and In Vitro Comparison with a Clinical-Stage Liposomal Formulation of MLP." Pharmaceutics 14, no. 7 (July 17, 2022): 1483. http://dx.doi.org/10.3390/pharmaceutics14071483.
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Nanomedicines have revolutionized the treatment of certain types of cancer, as is the case of doxil, liposomal formulation with doxorubicin encapsulated, in the treatment of certain types of ovarian cancer, AIDS-related Kaposi sarcoma, and multiple myeloma. These nanomedicines can improve the performance of conventional chemotherapeutic treatments, with fewer side effects and better efficiency against cancer. Although liposomes have been used in some formulations, different nanocarriers with better features in terms of stability and adsorption capabilities are being explored. Among the available nanoparticles in the field, mesoporous silica nanoparticles (MSNP) have attracted great attention as drug delivery platforms for the treatment of different diseases. Here, a novel formulation based on MSNP loaded with a potent antitumor prodrug that works in vitro as well as in a clinically evaluated liposomal formulation has been developed. This novel formulation shows excellent prodrug encapsulation efficiency and effective release of the anticancer drug only under certain stimuli typical of tumor environments. This behavior is of capital importance for translating this nanocarrier to the clinic in the near future.
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Gomes, Eliza Rocha, Fernanda Rezende Souza, Geovanni Dantas Cassali, Adriano de Paula Sabino, André Luis Branco de Barros, and Mônica Cristina Oliveira. "Investigation of the Antitumor Activity and Toxicity of Tumor-Derived Exosomes Fused with Long-Circulating and pH-Sensitive Liposomes Containing Doxorubicin." Pharmaceutics 14, no. 11 (October 22, 2022): 2256. http://dx.doi.org/10.3390/pharmaceutics14112256.
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Exosome–liposome hybrid nanocarriers containing chemotherapeutic agents have been developed to enhance drug delivery, improve the efficacy of the treatment of metastatic cancer, and overcome chemoresistance in cancer therapy. Thus, the objectives of this study were to investigate the toxicological profiles of exosomes fused with long-circulating and pH-sensitive liposomes containing doxorubicin (ExoSpHL-DOX) in healthy mice and the antitumor activity of ExoSpHL-DOX in Balb/c female mice bearing 4T1 breast tumors. The acute toxicity was determined by evaluating the mortality and morbidity of the animals and conducting hematological, biochemical, and histopathological analyses after a single intravenous administration of ExoSpHL-DOX. The results of the study indicated that the ExoSpHL-DOX treatment is less toxic than the free doxorubicin (DOX) treatment. ExoSpHL-DOX showed no signs of nephrotoxicity, even at the highest dose of DOX, indicating that the hybrid nanosystem may alter the distribution of DOX and reduce the kidney damage. Regarding the antitumor activity, ExoSpHL-DOX showed an antitumor effect compared to the control group. Furthermore, the hybrid nanocarrier of tumor-derived exosomes fused with long-circulating and pH-sensitive liposomes reduced the number of metastatic foci in the lungs. These results indicate that ExoSpHL-DOX may be a promising nanocarrier for the treatment of breast cancer, reducing toxicity and inhibiting metastasis, mainly in the lungs.
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Werengowska-Ciećwierz, Karolina, Marek Wiśniewski, Artur P. Terzyk, and Sylwester Furmaniak. "The Chemistry of Bioconjugation in Nanoparticles-Based Drug Delivery System." Advances in Condensed Matter Physics 2015 (2015): 1–27. http://dx.doi.org/10.1155/2015/198175.
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Nanomedicine is, generally, the application of nanotechnology to medicine. The term nanomedicine includes monitoring, construction of novel drug delivery systems, and any possible future applications of nanotechnology and nanovaccinology. In this review, the most important ligand-nanocarrier and drug-nanocarrier bioconjugations are described. The detailed characterizations of covalently formed bonds between targeted ligand and nanocarrier, including amide, thioether, disulfide, acetyl-hydrazone and polycyclic groups, are described. Also, the coupling of small elements and heteroatoms in the form of R-X-R the “click chemistry” groups is shown. Physical adsorption and chemical bonding of drug to nanocarrier surface involving drug on the internal or external surfaces of nanocarriers are described throughout possibility of the formation of the above-mentioned functionalities. Moreover, the most popular nanostructures (liposomes, micelles, polymeric nanoparticles, dendrimers, carbon nanotubes, and nanohorns) are characterized as nanocarriers. Building of modern drug carrier is a new method which could be effectively applied in targeted anticancer therapy.
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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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Mitchell, Michael J., Carlos A. Castellanos, and Michael R. King. "Nanostructured Surfaces to Target and Kill Circulating Tumor Cells While Repelling Leukocytes." Journal of Nanomaterials 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/831263.
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Hematogenous metastasis, the process of cancer cell migration from a primary to distal location via the bloodstream, typically leads to a poor patient prognosis. Selectin proteins hold promise in delivering drug-containing nanocarriers to circulating tumor cells (CTCs) in the bloodstream, due to their rapid, force-dependent binding kinetics. However, it is challenging to deliver such nanocarriers while avoiding toxic effects on healthy blood cells, as many possess ligands that adhesively interact with selectins. Herein, we describe a nanostructured surface to capture flowing cancer cells, while preventing human neutrophil adhesion. Microtube surfaces with immobilized halloysite nanotubes (HNTs) and E-selectin functionalized liposomal doxorubicin (ES-PEG L-DXR) significantly increased the number of breast adenocarcinoma MCF7 cells captured from flow, yet also significantly reduced the number of captured neutrophils. Neutrophils firmly adhered and projected pseudopods on surfaces coated only with liposomes, while neutrophils adherent to HNT-liposome surfaces maintained a round morphology. Perfusion of both MCF7 cells and neutrophils resulted in primarily cancer cell adhesion to the HNT-liposome surface, and induced significant cancer cell death. This work demonstrates that nanostructured surfaces consisting of HNTs and ES-PEG L-DXR can increase CTC recruitment for chemotherapeutic delivery, while also preventing healthy cell adhesion and uptake of therapeutic intended for CTCs.
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Rinaldi, Federica, Patrizia Nadia Hanieh, Simona Sennato, Federica De Santis, Jacopo Forte, Maurizio Fraziano, Stefano Casciardi, Carlotta Marianecci, Federico Bordi, and Maria Carafa. "Rifampicin–Liposomes for Mycobacterium abscessus Infection Treatment: Intracellular Uptake and Antibacterial Activity Evaluation." Pharmaceutics 13, no. 7 (July 13, 2021): 1070. http://dx.doi.org/10.3390/pharmaceutics13071070.
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Treatment of pulmonary infections caused by Mycobacterium abscessus are extremely difficult to treat, as this species is naturally resistant to many common antibiotics. Liposomes are vesicular nanocarriers suitable for hydrophilic and lipophilic drug loading, able to deliver drugs to the target site, and successfully used in different pharmaceutical applications. Moreover, liposomes are biocompatible, biodegradable and nontoxic vesicles and nebulized liposomes are efficient in targeting antibacterial agents to macrophages. The present aim was to formulate rifampicin-loaded liposomes (RIF–Lipo) for lung delivery, in order to increase the local concentration of the antibiotic. Unilamellar liposomal vesicles composed of anionic DPPG mixed with HSPC for rifampicin delivery were designed, prepared, and characterized. Samples were prepared by using the thin-film hydration method. RIF–Lipo and unloaded liposomes were characterized in terms of size, ζ-potential, bilayer features, stability and in different biological media. Rifampicin’s entrapment efficiency and release were also evaluated. Finally, biological activity of RIF-loaded liposomes in Mycobacterium abscessus-infected macrophages was investigated. The results show that RIF-lipo induce a significantly better reduction of intracellular Mycobacterium abscessus viability than the treatment with free drug. Liposome formulation of rifampicin may represent a valuable strategy to enhance the biological activity of the drug against intracellular mycobacteria.
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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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Palchetti, Sara, Damiano Caputo, Luca Digiacomo, Anna Capriotti, Roberto Coppola, Daniela Pozzi, and Giulio Caracciolo. "Protein Corona Fingerprints of Liposomes: New Opportunities for Targeted Drug Delivery and Early Detection in Pancreatic Cancer." Pharmaceutics 11, no. 1 (January 15, 2019): 31. http://dx.doi.org/10.3390/pharmaceutics11010031.
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Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer-related mortality in the Western world and is envisaged to become the second cause by 2030. Although our knowledge about the molecular biology of PDAC is continuously increasing, this progress has not been translated into better patients’ outcome. Liposomes have been used to circumvent concerns associated with the low efficiency of anticancer drugs such as severe side effects and damage of healthy tissues, but they have not resulted in improved efficacy as yet. Recently, the concept is emerging that the limited success of liposomal drugs in clinical practice is due to our poor knowledge of the nano–bio interactions experienced by liposomes in vivo. After systemic administration, lipid vesicles are covered by plasma proteins forming a biomolecular coating, referred to as the protein corona (PC). Recent studies have clarified that just a minor fraction of the hundreds of bound plasma proteins, referred to as “PC fingerprints” (PCFs), enhance liposome association with cancer cells, triggering efficient particle internalization. In this study, we synthesized a library of 10 liposomal formulations with systematic changes in lipid composition and exposed them to human plasma (HP). Size, zeta-potential, and corona composition of the resulting liposome–protein complexes were thoroughly characterized by dynamic light scattering (DLS), micro-electrophoresis, and nano-liquid chromatography tandem mass spectrometry (nano-LC MS/MS). According to the recent literature, enrichment in PCFs was used to predict the targeting ability of synthesized liposomal formulations. Here we show that the predicted targeting capability of liposome–protein complexes clearly correlate with cellular uptake in pancreatic adenocarcinoma (PANC-1) and insulinoma (INS-1) cells as quantified by flow-assisted cell sorting (FACS). Of note, cellular uptake of the liposomal formulation with the highest abundance of PCFs was much larger than that of Onivyde®, an Irinotecan liposomal drug approved by the Food and Drug Administration in 2015 for the treatment of metastatic PDAC. Given the urgent need of efficient nanocarriers for the treatment of PDAC, we envision that our results will pave the way for the development of more efficient PC-based targeted nanomaterials. Here we also show that some BCs are enriched with plasma proteins that are associated with the onset and progression of PDAC (e.g., sex hormone-binding globulin, Ficolin-3, plasma protease C1 inhibitor, etc.). This could open the intriguing possibility to identify novel biomarkers.
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Cadinoiu, Anca N., Delia M. Rata, Leonard I. Atanase, Oana M. Daraba, Daniela Gherghel, Gabriela Vochita, and Marcel Popa. "Aptamer-Functionalized Liposomes as a Potential Treatment for Basal Cell Carcinoma." Polymers 11, no. 9 (September 18, 2019): 1515. http://dx.doi.org/10.3390/polym11091515.
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More than one out of every three new cancers is a skin cancer, and the large majority are basal cell carcinomas (BCC). Targeted therapy targets the cancer’s specific genes, proteins, or tissue environment that contributes to cancer growth and survival and blocks the growth as well as the spread of cancer cells while limiting damage to healthy cells. Therefore, in the present study AS1411 aptamer-functionalized liposomes for the treatment of BCC were obtained and characterized. Aptamer conjugation increased liposome size, suggesting that the presence of an additional hydrophilic molecule on the liposomal surface increased the hydrodynamic diameter. As expected, the negatively charged DNA aptamer reduced the surface potential of the liposomes. Vertical Franz diffusion cells with artificial membranes were used to evaluate the in vitro release of 5-fluorouracil (5-FU). The aptamer moieties increase the stability of the liposomes and act as a supplementary steric barrier leading to a lower cumulative amount of the released 5-FU. The in vitro cell viability, targeting capability and apoptotic effects of liposomes on the human dermal fibroblasts and on the basal cell carcinoma TE 354.T cell lines were also evaluated. The results indicate that the functionalized liposomes are more efficient as nanocarriers than the non-functionalized ones.
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Reis, Priscila G., Adriana T. Abreu, Andrea G. Guimarães, Mônica C. Teixeira, Jacqueline de Souza, and Neila M. Silva-Barcellos. "Development and Validation of an Analytical Method for Quantification of Arsenic and Antimony in Liposomes Using Inductively Coupled Plasma-Optical Emission Spectrometry." Journal of AOAC INTERNATIONAL 96, no. 4 (July 1, 2013): 771–75. http://dx.doi.org/10.5740/jaoacint.10-263.
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Abstract Arsenic and antimony compounds are used to treat endemic diseases, such as cancer, leishmaniasis, and schistosomiasis, in spite of their toxicity. Several studies seeking the development and characterization of nanocarrier systems such as liposomes are being carried out with the aim of developing new drug delivery systems and minimizing the toxicity of these drugs. However, the lack of reference methods to quantify these semimetals within a liposomal matrix hinders the QC of these formulations. Therefore, the validation of an analytical method for arsenic and antimony quantification in liposomal matrix by inductively coupled plasma-optical emission spectrometry is presented here. The linearity, specificity, LOD, LOQ, accuracy, and precision were determined according to the International Conference on Harmonization norms and the Brazilian Health Surveillance Agency (Resolution 899). The LOD values were 0.02 and 0.06 mg/L for antimony and arsenic, respectively. The LOQ for both was 3.0 mg/L, with an adequate accuracy within 98.26 and 101.32% for different levels of antimony and 99.98 and 100.36% for arsenic. Precision (CV) was lower than 5.0%. The developed and validated method was shown to be reproducible for quantification of arsenic and antimony in liposome pharmaceutical dosage forms.
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Wang, Shile, Yanyu Chen, Jiancheng Guo, and Qinqin Huang. "Liposomes for Tumor Targeted Therapy: A Review." International Journal of Molecular Sciences 24, no. 3 (January 31, 2023): 2643. http://dx.doi.org/10.3390/ijms24032643.
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Liposomes, the most widely studied nano-drug carriers in drug delivery, are sphere-shaped vesicles consisting of one or more phospholipid bilayers. Compared with traditional drug delivery systems, liposomes exhibit prominent properties that include targeted delivery, high biocompatibility, biodegradability, easy functionalization, low toxicity, improvements in the sustained release of the drug it carries and improved therapeutic indices. In the wake of the rapid development of nanotechnology, the studies of liposome composition have become increasingly extensive. The molecular diversity of liposome composition, which includes long-circulating PEGylated liposomes, ligand-functionalized liposomes, stimuli-responsive liposomes, and advanced cell membrane-coated biomimetic nanocarriers, endows their drug delivery with unique physiological functions. This review describes the composition, types and preparation methods of liposomes, and discusses their targeting strategies in cancer therapy.
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Yang, Meng, Yongwei Gu, Xiaomeng Tang, Ting Wang, and Jiyong Liu. "Advancement of Lipid-Based Nanocarriers and Combination Application with Physical Penetration Technique." Current Drug Delivery 16, no. 4 (April 10, 2019): 312–24. http://dx.doi.org/10.2174/1567201816666190118125427.
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On account of the advantages of transdermal delivery and the application situation of transcutaneous technology in transdermal delivery, the article critically comments on nanosystems as permeation enhancement model. Nanosystems possess great potential for transcutaneous drug delivery. This review focuses on recent advances in lipid-based nanocarriers, including liposome, transfersomes, ethosomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers and combination application of the lipid-based nanocarriers with microneedle, iontophoresis, electroporation and sonophoresis in the field for the development of the transdermal drug delivery system. We attempted to give an overview of lipid-based nanocarriers with the aim to improve transdermal and dermal drug delivery. A special focus is given to the nanocarrier composition, characteristic and interaction mechanisms through the skin. Recent combination applications of lipid-based nanocarriers with the physical penetration technology demonstrate the superiority of the combined use of nanocarriers and physical methods in drug penetration enhancement compared to their single use. In the future, lipidbased nanocarriers will play a greater role in the field of transdermal and dermal drug delivery.
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Torchilin, V. P. "Tatp-mediated intracellular delivery of pharmaceutical nanocarriers." Biochemical Society Transactions 35, no. 4 (July 20, 2007): 816–20. http://dx.doi.org/10.1042/bst0350816.
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CPPs (cell-penetrating peptides), including Tatp (transactivator of transcription peptide), have been successfully used for intracellular delivery of a wide variety of cargoes including various nanoparticulate pharmaceutical carriers such as liposomes, micelles and nanoparticles. Here, we will consider the major results obtained in this area with emphasis on Tatp-mediated delivery of liposomes and various transfection vectors. We will also address the development of ‘smart’ stimuli-sensitive nanocarriers, where the cell-penetrating function can only be activated when the nanocarrier is inside the biological target, thus minimizing the interaction with non-target cells.
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Shakouri, Amir, Houman Kahroba, Hamed Hamishekar, and Jalal Abdolalizadeh. "Nanoencapsulation of Hirudo medicinalis proteins in liposomes as a nanocarrier for inhibiting angiogenesis through targeting VEGFA in the Breast cancer cell line (MCF-7)." BioImpacts 12, no. 2 (August 9, 2021): 115–26. http://dx.doi.org/10.34172/bi.2021.39.
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Introduction: Breast cancer is the most serious cause of women’s death throughout the world. Using nanocarrier vehicles to the exact site of cancer upgrades the therapeutic efficiency of the drugs. Capsulation of active proteins in the vesicular liposomes’ hydrophilic core is essential to develop a therapeutic protein carrier system. We aimed to encapsulate the medicinal leech saliva extract (LSE) and assess the inhibition of angiogenesis of breast cancer cells by targeting vascular endothelial growth factor A (VEGFA). Methods: In this research, enhanced formulation of liposomal protein was determined by zeta potential analysis, droplet size, drug release assay, and transmission electron microscopy (TEM). Furthermore, a cytotoxicity assay of liposomal LSE was performed to determine the cytotoxic activity of components. For assessing the expression of VEGFA, P53, and hypoxia-inducible factor subunit alpha (HIF1a) genes, Real-Time PCR was applied. Results: Nano liposome was chosen as an enhanced formulation due to its much smaller size (46.23 nm). Liposomal LSE had more practical actions on the MCF-7 cells. As noticed by DAPI staining, apoptosis was extensively greater in treated MCF-7 cells. Wound healing assay demonstrated that MCF-7 cells could not sustain growth at the presence of liposomal LSE and expression of the VEGFA gene was declined in treated cells. Downregulation of VEGFA was evaluated with western blotting technique. Conclusion: It can be concluded that our investigation of the tests confirmed the fact that nano liposomal LSE is a novel promising formulation for anticancer drugs and can significantly improve the penetration of protein drugs to cancer cells.
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Nishida, Shogo, Yuuki Takashima, Ryotaro Udagawa, Hisako Ibaraki, Yasuo Seta, and Hiroshi Ishihara. "A Multifunctional Hybrid Nanocarrier for Non-Invasive siRNA Delivery to the Retina." Pharmaceutics 15, no. 2 (February 11, 2023): 611. http://dx.doi.org/10.3390/pharmaceutics15020611.
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Drug therapy for retinal diseases (e.g., age-related macular degeneration, the leading cause of blindness) is generally performed by invasive intravitreal injection because of poor drug delivery caused by the blood–retinal barrier (BRB). This study aimed to develop a nanocarrier for the non-invasive delivery of small interfering RNA (siRNA) to the posterior segment of the eye (i.e., the retina) by eyedrops. To this end, we prepared a hybrid nanocarrier based on a multifunctional peptide and liposomes, and the composition was optimized. A cytoplasm-responsive stearylated peptide (STR-CH2R4H2C) was used as the multifunctional peptide because of its superior ability to enhance the complexation, cell permeation, and intracellular dynamics of siRNA. By adding STR-CH2R4H2C to the surface of liposomes, intracellular uptake increased regardless of the liposome surface charge. The STR-CH2R4H2C-modified cationic nanocarrier demonstrated significant siRNA transfection efficiency with no cytotoxicity, enhanced siRNA release from endosomes, and effectively suppressed vascular endothelial growth factor expression in rat retinal pigment epithelium cells. The 2.0 mol% STR-CH2R4H2C-modified cationic nanocarrier enhanced intraocular migration into the retina after instillation into rat eyes.
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RAMLI, NUR AMALINA, NORA’AINI ALI, and SOFIAH HAMZAH. "PHYSICOCHEMICAL CHARACTERIZATION OF QUERCETIN-LOADED LIPOSOMES PREPARED BY SONICATION FOR FUNCTIONAL FOOD APPLICATION." Journal of Sustainability Science and Management 15, no. 6 (August 30, 2020): 15–27. http://dx.doi.org/10.46754/jbsd.2020.08.002.
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This research was intended to synthesize liposome as a nanocarrier to encapsulate quercetin, which is prone to degradation and susceptible to low bioavailability upon oral administration. The liposomes were synthesized by thin-film hydration method and followed by probe sonication for downsizing. Soy phosphatidylcholine (SPC) and cholesterol (CHOL) were employed as the composition of the phospholipid bilayer. Results indicated a dependence of sonication amplitude and time in the formation of free liposomes (FL). The average size of quercetin-loaded liposomes (QL) prepared was 346.4 nm with a narrow polydispersity index (0.22) and a high magnitude of zeta potential (-49.6 mV). These characterizations depict that a homogenous nanovesicle suspension with high stability was successfully synthesized. Quercetin was incorporated into the liposomes with a high encapsulation efficiency of 90.7% and loading capacity of 9.3%. This viable nanocarrier perhaps will provide ingenious protection for a wider spectrum of active agents in food and biopharmaceutical products.
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Ibaraki, Hisako, Akihiro Takeda, Naoki Arima, Naruhiro Hatakeyama, Yuuki Takashima, Yasuo Seta, and Takanori Kanazawa. "In Vivo Fluorescence Imaging of Passive Inflammation Site Accumulation of Liposomes via Intravenous Administration Focused on Their Surface Charge and PEG Modification." Pharmaceutics 13, no. 1 (January 14, 2021): 104. http://dx.doi.org/10.3390/pharmaceutics13010104.
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Nanocarriers such as liposomes have been attracting attention as novel therapeutic methods for inflammatory autoimmune diseases such as rheumatoid arthritis and ulcerative colitis. The physicochemical properties of intravenously administered nanomedicines enable them to target inflamed tissues passively. However, few studies have attempted to determine the influences of nanoparticle surface characteristics on inflammation site accumulation. Here, we aimed to study the effects of polyethylene glycol (PEG) modification and surface charge on liposome ability to accumulate in inflammatory sites and be uptake by macrophages. Four different liposome samples with different PEG modification and surface charge were prepared. Liposome accumulation in the inflammation sites of arthritis and ulcerative colitis model mice was evaluated by using in vivo imaging. There was greater PEG-modified than unmodified liposome accumulation at all inflammation sites. There was greater anionic than cationic liposome accumulation at all inflammation sites. The order in which inflammation site accumulation was confirmed was PEG-anionic > PEG-cationic > anionic > cationic. PEG-anionic liposomes had ~2.5× higher fluorescence intensity than PEG-cationic liposomes, and the PEG-liposomes had ~2× higher fluorescence intensity than non-PEG liposomes. All liposomes have not accumulated at the inflammation sites in healthy mice. Furthermore, cationic liposomes were taken up to ~10× greater extent by RAW264.7 murine macrophages. Thus, PEG-cationic liposomes that have the ability to accumulate in inflammatory sites via intravenous administration and to be taken up by macrophages could be useful.
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Mishra, Keerti, and Akhlesh K. Jain. "Liposomes: An Emerging Approach for the Treatment of Cancer." Current Pharmaceutical Design 27, no. 20 (August 4, 2021): 2398–414. http://dx.doi.org/10.2174/1381612827666210406141449.
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Background: Conventional drug delivery agents for a life-threatening disease, i.e., cancer, lack specificity towards cancer cells, producing a greater degree of side effects in the normal cells with a poor therapeutic index. These toxic side effects often limit dose escalation of anti-cancer drugs, leading to incomplete tumor suppression/ cancer eradication, early disease relapse, and ultimately, the development of drug resistance. Accordingly, targeting the tumor vasculatures is essential for the treatment of cancer. Objective: To search and describe a safer drug delivery carrier for the treatment of cancer with reduced systemic toxicities. Methods: Data were collected from Medline, PubMed, Google Scholar, Science Direct using the following keywords: ‘liposomes’, ‘nanocarriers’, ‘targeted drug delivery’, ‘ligands’, ‘liposome for anti-cancerous drugs’, ‘treatment for cancer’ and ‘receptor targeting.’ Results: Liposomes have provided a safe platform for the targeted delivery of encapsulated anti-cancer drugs for the treatment of cancer, which results in the reduction of the cytotoxic side effects of anti-cancer drugs on normal cells. Conclusion: Liposomal targeting is a better emerging approach as an advanced drug delivery carrier with targeting ligands for anti-cancer agents.
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Malliappan, Sivakumar P., Palanivel Kandasamy, Siva Chidambaram, Devanand Venkatasubbu, Sathish K. Perumal, and Abimanyu Sugumaran. "Breast Cancer Targeted Treatment Strategies: Promising Nanocarrier Approaches." Anti-Cancer Agents in Medicinal Chemistry 20, no. 11 (July 8, 2020): 1300–1310. http://dx.doi.org/10.2174/1871520619666191022175003.
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Breast cancer is the second most common cancer that causes death among women worldwide. Incidence of breast cancer is increasing worldwide, and the age at which breast cancer develops has shifted from 50- 70 years to 30-40 years. Chemotherapy is the most commonly used effective treatment strategy to combat breast cancer. However, one of the major drawbacks is low selective site-specificity and the consequent toxic insult to normal healthy cells. The nanocarrier system is consistently utilised to minimise the various limitations involved in the conventional treatment of breast cancer. The nanocarrier based targeted drug delivery system provides better bioavailability, prolonged circulation with an effective accumulation of drugs at the tumour site either by active or passive drug targeting. Active targeting has been achieved by receptor/protein anchoring and externally guided magnetic nanocarriers, whereas passive targeting accomplished by employing the access to the tunnel via leaky tumour vasculature, utilising the tumour microenvironment, because the nanocarrier systems can reduce the toxicity to normal cells. As of now a few nanocarrier systems have been approved by FDA, and various nanoformulations are in the pipeline at the preclinical and clinical development for targeting breast cancer; among them, polymeric micelles, microemulsions, magnetic microemulsions, liposomes, dendrimers, carbon nanotubes, and magnetic Nanoparticles (NPs) are the most common. The current review highlights the active and passive targeting potential of nanocarriers in breast cancer and discusses their role in targeting breast cancer without affecting normal healthy cells.
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Kenchegowda, Madhuchandra, Mohamed Rahamathulla, Umme Hani, Mohammed Y. Begum, Sagar Guruswamy, Riyaz Ali M. Osmani, Mysore P. Gowrav, et al. "Smart Nanocarriers as an Emerging Platform for Cancer Therapy: A Review." Molecules 27, no. 1 (December 27, 2021): 146. http://dx.doi.org/10.3390/molecules27010146.
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Cancer is a group of disorders characterized by uncontrolled cell growth that affects around 11 million people each year globally. Nanocarrier-based systems are extensively used in cancer imaging, diagnostics as well as therapeutics; owing to their promising features and potential to augment therapeutic efficacy. The focal point of research remains to develop new-fangled smart nanocarriers that can selectively respond to cancer-specific conditions and deliver medications to target cells efficiently. Nanocarriers deliver loaded therapeutic cargos to the tumour site either in a passive or active mode, with the least drug elimination from the drug delivery systems. This review chiefly focuses on current advances allied to smart nanocarriers such as dendrimers, liposomes, mesoporous silica nanoparticles, quantum dots, micelles, superparamagnetic iron-oxide nanoparticles, gold nanoparticles and carbon nanotubes, to list a few. Exhaustive discussion on crucial topics like drug targeting, surface decorated smart-nanocarriers and stimuli-responsive cancer nanotherapeutics responding to temperature, enzyme, pH and redox stimuli have been covered.
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Lombardo, Domenico, and Mikhail A. Kiselev. "Methods of Liposomes Preparation: Formation and Control Factors of Versatile Nanocarriers for Biomedical and Nanomedicine Application." Pharmaceutics 14, no. 3 (February 28, 2022): 543. http://dx.doi.org/10.3390/pharmaceutics14030543.
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Liposomes are nano-sized spherical vesicles composed of an aqueous core surrounded by one (or more) phospholipid bilayer shells. Owing to their high biocompatibility, chemical composition variability, and ease of preparation, as well as their large variety of structural properties, liposomes have been employed in a large variety of nanomedicine and biomedical applications, including nanocarriers for drug delivery, in nutraceutical fields, for immunoassays, clinical diagnostics, tissue engineering, and theranostics formulations. Particularly important is the role of liposomes in drug-delivery applications, as they improve the performance of the encapsulated drugs, reducing side effects and toxicity by enhancing its in vitro- and in vivo-controlled delivery and activity. These applications stimulated a great effort for the scale-up of the formation processes in view of suitable industrial development. Despite the improvements of conventional approaches and the development of novel routes of liposome preparation, their intrinsic sensitivity to mechanical and chemical actions is responsible for some critical issues connected with a limited colloidal stability and reduced entrapment efficiency of cargo molecules. This article analyzes the main features of the formation and fabrication techniques of liposome nanocarriers, with a special focus on the structure, parameters, and the critical factors that influence the development of a suitable and stable formulation. Recent developments and new methods for liposome preparation are also discussed, with the objective of updating the reader and providing future directions for research and development.
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Sapino, Simona, Giulia Chindamo, Daniela Chirio, Silvia Morel, Elena Peira, Cristina Vercelli, and Marina Gallarate. "Nanocarriers in Veterinary Medicine: A Challenge for Improving Osteosarcoma Conventional Treatments." Nanomaterials 12, no. 24 (December 19, 2022): 4501. http://dx.doi.org/10.3390/nano12244501.
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In recent years, several nanocarrier-based drug delivery systems, such as polymeric nanoparticles, solid lipid nanoparticles, metallic nanoparticles, liposomes, and others, have been explored to target and treat a wide variety of diseases. Their employment has brought many benefits, not only to human medicine but also to veterinary medicine, albeit at a slower rate. Soon, the use of nanocarriers could revolutionize the animal health sector, and many veterinary therapies will be more effective as a result. The purpose of this review is to offer an overview of the main applications of nanocarriers in the veterinary field, from supplements for animal health and reproduction to nanovaccines and nanotherapies. Among the major pathologies that can affect animals, special attention is given to canine osteosarcoma (OSA): a comparison with human OSA is provided and the main treatment options are reviewed emphasizing the benefits that nanocarriers could bring in the treatment of this widespread disease.
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Zafar, Mah Noor, Waad H. Abuwatfa, and Ghaleb A. Husseini. "Acoustically-Activated Liposomal Nanocarriers to Mitigate the Side Effects of Conventional Chemotherapy with a Focus on Emulsion-Liposomes." Pharmaceutics 15, no. 2 (January 27, 2023): 421. http://dx.doi.org/10.3390/pharmaceutics15020421.
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To improve currently available cancer treatments, nanomaterials are employed as smart drug delivery vehicles that can be engineered to locally target cancer cells and respond to stimuli. Nanocarriers can entrap chemotherapeutic drugs and deliver them to the diseased site, reducing the side effects associated with the systemic administration of conventional anticancer drugs. Upon accumulation in the tumor cells, the nanocarriers need to be potentiated to release their therapeutic cargo. Stimulation can be through endogenous or exogenous modalities, such as temperature, electromagnetic irradiation, ultrasound (US), pH, or enzymes. This review discusses the acoustic stimulation of different sonosensitive liposomal formulations. Emulsion liposomes, or eLiposomes, are liposomes encapsulating phase-changing nanoemulsion droplets, which promote acoustic droplet vaporization (ADV) upon sonication. This gives eLiposomes the advantage of delivering the encapsulated drug at low intensities and short exposure times relative to liposomes. Other formulations integrating microbubbles and nanobubbles are also discussed.
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Mühlberg, Eric, Mira Burtscher, Florian Umstätter, Gert Fricker, Walter Mier, and Philipp Uhl. "Trends in liposomal nanocarrier strategies for the oral delivery of biologics." Nanomedicine 16, no. 20 (August 2021): 1813–32. http://dx.doi.org/10.2217/nnm-2021-0177.
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The number of approved macromolecular drugs such as peptides, proteins and antibodies steadily increases. Since drugs with high molecular weight are commonly not suitable for oral delivery, research on carrier strategies enabling oral administration is of vital interest. In past decades, nanocarriers, in particular liposomes, have been exhaustively investigated as oral drug-delivery platform. Despite their successful application as parenteral delivery vehicles, liposomes have up to date not succeeded for oral administration. However, a plenitude of approaches aiming to increase the oral bioavailability of macromolecular drugs administered by liposomal formulations has been published. Here, we summarize the strategies published in the last 10 years (vaccine strategies excluded) with a main focus on strategies proven efficient in animal models.
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Zarrabi, Ali, Atefeh Zarepour, Arezoo Khosravi, Zahra Alimohammadi, and Vijay Kumar Thakur. "Synthesis of Curcumin Loaded Smart pH-Responsive Stealth Liposome as a Novel Nanocarrier for Cancer Treatment." Fibers 9, no. 3 (March 8, 2021): 19. http://dx.doi.org/10.3390/fib9030019.
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The innovation of drug delivery vehicles with controlled properties for cancer therapy is the aim of most pharmaceutical research. This study aims to fabricate a new type of smart biocompatible stealth-nanoliposome to deliver curcumin for cancer treatment. Herein, four different types of liposomes (with/without pH-responsive polymeric coating) were synthesized via the Mozafari method and then characterized with several tests, including dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), Zeta potential, and field emission scanning electron microscopes (FE-S EM). The loading and release profile of curcumin were evaluated in two pH of 7.4 and 6.6. Finally, the MTT assay was used to assess the cytotoxicity of the samples. FE-SEM results revealed a mean size of about 40 and 50 nm for smart stealth-liposome and liposome, respectively. The results of drug entrapment revealed that non-coated liposome had about 74% entrapment efficiency, while it was about 84% for PEGylated liposomes. Furthermore, the drug released pattern of the nanocarriers showed more controllable release in stealth-liposome in comparison to non-coated one. The results of the cytotoxicity test demonstrated the toxicity of drug-loaded carriers on cancer cells. Based on the results of this study, the as-prepared smart stealth pH-responsive nanoliposome could be considered as a potential candidate for cancer therapy.
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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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Naziris, Nikolaos, Natassa Pippa, Evangelia Sereti, Varvara Chrysostomou, Marta Kędzierska, Jakub Kajdanek, Maksim Ionov, et al. "Chimeric Stimuli-Responsive Liposomes as Nanocarriers for the Delivery of the Anti-Glioma Agent TRAM-34." International Journal of Molecular Sciences 22, no. 12 (June 10, 2021): 6271. http://dx.doi.org/10.3390/ijms22126271.
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Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells.
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Veselov, Valery V., Alexander E. Nosyrev, László Jicsinszky, Renad N. Alyautdin, and Giancarlo Cravotto. "Targeted Delivery Methods for Anticancer Drugs." Cancers 14, no. 3 (January 26, 2022): 622. http://dx.doi.org/10.3390/cancers14030622.
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Several drug-delivery systems have been reported on and often successfully applied in cancer therapy. Cell-targeted delivery can reduce the overall toxicity of cytotoxic drugs and increase their effectiveness and selectivity. Besides traditional liposomal and micellar formulations, various nanocarrier systems have recently become the focus of developmental interest. This review discusses the preparation and targeting techniques as well as the properties of several liposome-, micelle-, solid-lipid nanoparticle-, dendrimer-, gold-, and magnetic-nanoparticle-based delivery systems. Approaches for targeted drug delivery and systems for drug release under a range of stimuli are also discussed.
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Tziveleka, Leto-Aikaterini, Natassa Pippa, Efstathia Ioannou, Costas Demetzos, and Vassilios Roussis. "Development of Ulvan-Containing Liposomes as Antibacterial Drug Delivery Platforms." Journal of Functional Biomaterials 13, no. 4 (October 13, 2022): 186. http://dx.doi.org/10.3390/jfb13040186.
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Liposomes, due to their safety profile and targeting ability, are among the most studied nanocarriers as antimicrobial delivery systems. However, due to lack of stability and the non-specific interaction of liposomes with cells and proteins, their use is relatively limited. Aiming to overcome these drawbacks, it was envisaged that incorporation of ulvan, a bioactive marine sulfated polysaccharide isolated from green algae, in liposomes could improve their physicochemical properties and overall stability. Thus, we initially studied the interactions of ulvan with neutral, negatively, and positively charged lipids using Differential Scanning Calorimetry and subsequently, based on the obtained results, we prepared the respective ulvan–containing neutral and charged liposomes, where ulvan interacts with both lipid chains and polar groups in the liposomal bilayer. In a further step, we entrapped in the liposomes fusidic acid, used as a model antibacterial drug, and proceeded with the evaluation of their antibacterial activity against Staphylococcus aureus. The physicochemical properties (size and ζ-potential), stability, morphology, and entrapment efficiency of the prepared liposomal formulations were determined.
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Pamornpathomkul, Boonnada, Worranan Rangsimawong, Theerasak Rojanarata, Praneet Opanasopit, Chuleerath Chaiyodsilp, and Tanasait Ngawhirunpat. "Lipid-based nanocarriers to enhance skin permeation and antioxidant activity of Centella asiatica extract." MATEC Web of Conferences 192 (2018): 01016. http://dx.doi.org/10.1051/matecconf/201819201016.
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The purpose of this study was to evaluate the use of different formulations, including solution, gel, liposome and niosome for in vitro skin permeation and antioxidant activity of Centella asiatica (CA) extract. The liposomes and niosomes loaded with CA were characterized to observe the physicochemical properties i.e., particle size, zeta potential, percentage of entrapment efficiency (%EE) and percentage of loading efficiency (%LE). In vitro skin permeation studies revealed that liposome formulations had a superior enhancing effect on skin permeation compared to niosome, gel and solution formulation. Upon applied niosome formulations for the delivery of CA extract at 24 hours (h), the antioxidant activity was higher than liposome, gel and solution formulation, as evidenced by the increased in percent inhibition using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. However, there was no significant difference in antioxidant activity between niosome and liposome formulations. Accordingly, both the liposome and noisome formulations are promising approaches for transdermal delivery of CA extract for promoting successful antioxidant activity.
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Piwowarczyk, Ludwika, Dariusz T. Mlynarczyk, Violetta Krajka-Kuźniak, Aleksandra Majchrzak-Celińska, Anna Budzianowska, Szymon Tomczak, Jaromir Budzianowski, et al. "Natural Compounds in Liposomal Nanoformulations of Potential Clinical Application in Glioblastoma." Cancers 14, no. 24 (December 16, 2022): 6222. http://dx.doi.org/10.3390/cancers14246222.
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Glioblastoma (GBM) is the most common malignant neoplasm in adults among all CNS gliomas, with the 5-year survival rate being as low as 5%. Among nanocarriers, liposomal nanoformulations are considered as a promising tool for precise drug delivery. The herein presented study demonstrates the possibility of encapsulating four selected natural compounds (curcumin, bisdemethoxycurcumin, acteoside, and orientin) and their mixtures in cationic liposomal nanoformulation composed of two lipid types (DOTAP:POPC). In order to determine the physicochemical properties of the new drug carriers, specific measurements, including particle size, Zeta Potential, and PDI index, were applied. In addition, NMR and EPR studies were carried out for a more in-depth characterization of nanoparticles. Within biological research, the prepared formulations were evaluated on T98G and U-138 MG glioblastoma cell lines in vitro, as well as on a non-cancerous human lung fibroblast cell line (MRC-5) using the MTT test to determine their potential as anticancer agents. The highest activity was exhibited by liposome-entrapped acteoside towards the T98G cell line with IC50 equal 2.9 ± 0.9 µM after 24 hours of incubation. Noteworthy, curcumin and orientin mixture in liposomal formulation exhibited a synergistic effect against GBM. Moreover, the impact on the expression of apoptosis-associated proteins (p53 and Caspase-3) of acteoside as well as curcumin and orientin mixture, as the most potent agents, was assessed, showing nearly 40% increase as compared to control U-138 MG and T98G cells. It should be emphasized that a new and alternative method of extrusion of the studied liposomes was developed.
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Bahutair, Wafa N., Waad H. Abuwatfa, and Ghaleb A. Husseini. "Ultrasound Triggering of Liposomal Nanodrugs for Cancer Therapy: A Review." Nanomaterials 12, no. 17 (September 2, 2022): 3051. http://dx.doi.org/10.3390/nano12173051.
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Efficient conventional chemotherapy is limited by its nonspecific nature, which causes severe systemic toxicity that can lead to patient discomfort and low therapeutic efficacy. The emergence of smart drug delivery systems (SDDSs) utilizing nanoparticles as drug nanocarriers has shown great potential in enhancing the targetability of anticancer agents and limiting their side effects. Liposomes are among the most investigated nanoplatforms due to their promising capabilities of encapsulating hydrophilic, lipophilic, and amphiphilic drugs, biocompatibility, physicochemical and biophysical properties. Liposomal nanodrug systems have demonstrated the ability to alter drugs’ biodistribution by sufficiently delivering the entrapped chemotherapeutics at the targeted diseased sites, sparing normal cells from undesired cytotoxic effects. Combining liposomal treatments with ultrasound, as an external drug release triggering modality, has been proven effective in spatially and temporally controlling and stimulating drug release. Therefore, this paper reviews recent literature pertaining to the therapeutic synergy of triggering nanodrugs from liposomes using ultrasound. It also highlights the effects of multiple physical and chemical factors on liposomes’ sonosensetivity, several ultrasound-induced drug release mechanisms, and the efficacy of ultrasound-responsive liposomal systems in cancer therapy. Overall, liposomal nanodrug systems triggered by ultrasound are promising cancer therapy platforms that can potentially alleviate the detriments of conventional cancer treatments.
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Gomes, Eliza Rocha, and Marina Santiago Franco. "Combining Nanocarrier-Assisted Delivery of Molecules and Radiotherapy." Pharmaceutics 14, no. 1 (January 3, 2022): 105. http://dx.doi.org/10.3390/pharmaceutics14010105.
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Cancer is responsible for a significant proportion of death all over the world. Therefore, strategies to improve its treatment are highly desired. The use of nanocarriers to deliver anticancer treatments has been extensively investigated and improved since the approval of the first liposomal formulation for cancer treatment in 1995. Radiotherapy (RT) is present in the disease management strategy of around 50% of cancer patients. In the present review, we bring the state-of-the-art information on the combination of nanocarrier-assisted delivery of molecules and RT. We start with formulations designed to encapsulate single or multiple molecules that, once delivered to the tumor site, act directly on the cells to improve the effects of RT. Then, we describe formulations designed to modulate the tumor microenvironment by delivering oxygen or to boost the abscopal effect. Finally, we present how RT can be employed to trigger molecule delivery from nanocarriers or to modulate the EPR effect.
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Elkhoury, Kamil, Polen Koçak, Alex Kang, Elmira Arab-Tehrany, Jennifer Ellis Ward, and Su Ryon Shin. "Engineering Smart Targeting Nanovesicles and Their Combination with Hydrogels for Controlled Drug Delivery." Pharmaceutics 12, no. 9 (September 7, 2020): 849. http://dx.doi.org/10.3390/pharmaceutics12090849.
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Smart engineered and naturally derived nanovesicles, capable of targeting specific tissues and cells and delivering bioactive molecules and drugs into them, are becoming important drug delivery systems. Liposomes stand out among different types of self-assembled nanovesicles, because of their amphiphilicity and non-toxic nature. By modifying their surfaces, liposomes can become stimulus-responsive, releasing their cargo on demand. Recently, the recognized role of exosomes in cell-cell communication and their ability to diffuse through tissues to find target cells have led to an increase in their usage as smart delivery systems. Moreover, engineering “smarter” delivery systems can be done by creating hybrid exosome-liposome nanocarriers via membrane fusion. These systems can be loaded in naturally derived hydrogels to achieve sustained and controlled drug delivery. Here, the focus is on evaluating the smart behavior of liposomes and exosomes, the fabrication of hybrid exosome-liposome nanovesicles, and the controlled delivery and routes of administration of a hydrogel matrix for drug delivery systems.
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Lombardo, Domenico, Mikhail A. Kiselev, and Maria Teresa Caccamo. "Smart Nanoparticles for Drug Delivery Application: Development of Versatile Nanocarrier Platforms in Biotechnology and Nanomedicine." Journal of Nanomaterials 2019 (February 27, 2019): 1–26. http://dx.doi.org/10.1155/2019/3702518.
Full textAbstract:
The study of nanostructured drug delivery systems allows the development of novel platforms for the efficient transport and controlled release of drug molecules in the harsh microenvironment of diseased tissues of living systems, thus offering a wide range of functional nanoplatforms for smart application in biotechnology and nanomedicine. This article highlights recent advances of smart nanocarriers composed of organic (including polymeric micelles and vesicles, liposomes, dendrimers, and hydrogels) and inorganic (including quantum dots, gold and mesoporous silica nanoparticles) materials. Despite the remarkable developments of recent synthetic methodologies, most of all nanocarriers’ action is associated with a number of unwanted side effects that diminish their efficient use in biotechnology and nanomedicine applications. This highlights some critical issues in the design and engineering of nanocarrier systems for biotechnology applications, arising from the complex environment and multiform interactions established within the specific biological media.
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Perche, Federico, and Vladimir P. Torchilin. "Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting." Journal of Drug Delivery 2013 (March 7, 2013): 1–32. http://dx.doi.org/10.1155/2013/705265.
Full textAbstract:
Liposomes are delivery systems that have been used to formulate a vast variety of therapeutic and imaging agents for the past several decades. They have significant advantages over their free forms in terms of pharmacokinetics, sensitivity for cancer diagnosis and therapeutic efficacy. The multifactorial nature of cancer and the complex physiology of the tumor microenvironment require the development of multifunctional nanocarriers. Multifunctional liposomal nanocarriers should combine long blood circulation to improve pharmacokinetics of the loaded agent and selective distribution to the tumor lesion relative to healthy tissues, remote-controlled or tumor stimuli-sensitive extravasation from blood at the tumor’s vicinity, internalization motifs to move from tumor bounds and/or tumor intercellular space to the cytoplasm of cancer cells for effective tumor cell killing. This review will focus on current strategies used for cancer detection and therapy using liposomes with special attention to combination therapies.
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Sharma, Shubham, Lilly Mulrey, Megan Byrne, Amit K. Jaiswal, and Swarna Jaiswal. "Encapsulation of Essential Oils in Nanocarriers for Active Food Packaging." Foods 11, no. 15 (August 5, 2022): 2337. http://dx.doi.org/10.3390/foods11152337.
Full textAbstract:
Active packaging improves a packaging system’s effectiveness by actively integrating additional components into the packaging material or the headspace around the packaging. Consumer demand and awareness have grown enough to replace chemical agents with natural active agents. Essential oils (EOs) are extensively distributed throughout nature but at low levels and sometimes with poor recovery yields, which poses an issue with their application in food. Due to the instability of EOs when added directly into a food product, they require encapsulation before being added to a packaging matrix such as liposomes, solid-lipid nanoparticles, nano-emulsions, cyclodextrins, and nanostructured lipid nano-carriers. This article is focused on the encapsulation of EOs in different types of nanocarriers. Nanocarriers can improve the efficiency of active substances by providing protection, stability, and controlled and targeted release. The advantages of the many types of nanocarriers that contain active substances that can be used to make antibacterial and antioxidant biopolymeric-based active packaging are discussed. A nanocarrier-encapsulated EO enables the controlled release of oil, stabilizing the packaging for a longer duration.
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Liang, Pan, Linshen Mao, Yanli Dong, Zhenwen Zhao, Qin Sun, Maryam Mazhar, Yining Ma, Sijin Yang, and Wei Ren. "Design and Application of Near-Infrared Nanomaterial-Liposome Hybrid Nanocarriers for Cancer Photothermal Therapy." Pharmaceutics 13, no. 12 (December 3, 2021): 2070. http://dx.doi.org/10.3390/pharmaceutics13122070.
Full textAbstract:
Liposomes are attractive carriers for targeted and controlled drug delivery receiving increasing attention in cancer photothermal therapy. However, the field of creating near-infrared nanomaterial-liposome hybrid nanocarriers (NIRN-Lips) is relatively little understood. The hybrid nanocarriers combine the dual superiority of nanomaterials and liposomes, with more stable particles, enhanced photoluminescence, higher tumor permeability, better tumor-targeted drug delivery, stimulus-responsive drug release, and thus exhibiting better anti-tumor efficacy. Herein, this review covers the liposomes supported various types of near-infrared nanomaterials, including gold-based nanomaterials, carbon-based nanomaterials, and semiconductor quantum dots. Specifically, the NIRN-Lips are described in terms of their feature, synthesis, and drug-release mechanism. The design considerations of NIRN-Lips are highlighted. Further, we briefly introduced the photothermal conversion mechanism of NIRNs and the cell death mechanism induced by photothermal therapy. Subsequently, we provided a brief conclusion of NIRNs-Lips applied in cancer photothermal therapy. Finally, we discussed a synopsis of associated challenges and future perspectives for the applications of NIRN-Lips in cancer photothermal therapy.
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Argenziano, Monica, Silvia Arpicco, Paola Brusa, Roberta Cavalli, Daniela Chirio, Franco Dosio, Marina Gallarate, Elena Peira, Barbara Stella, and Elena Ugazio. "Developing Actively Targeted Nanoparticles to Fight Cancer: Focus on Italian Research." Pharmaceutics 13, no. 10 (September 22, 2021): 1538. http://dx.doi.org/10.3390/pharmaceutics13101538.
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Active targeting is a valuable and promising approach with which to enhance the therapeutic efficacy of nanodelivery systems, and the development of tumor-targeted nanoparticles has therefore attracted much research attention. In this field, the research carried out in Italian Pharmaceutical Technology academic groups has been focused on the development of actively targeted nanosystems using a multidisciplinary approach. To highlight these efforts, this review reports a thorough description of the last 10 years of Italian research results on the development of actively targeted nanoparticles to direct drugs towards different receptors that are overexpressed on cancer cells or in the tumor microenvironment. In particular, the review discusses polymeric nanocarriers, liposomes, lipoplexes, niosomes, solid lipid nanoparticles, squalene nanoassemblies and nanobubbles. For each nanocarrier, the main ligands, conjugation strategies and target receptors are described. The literature indicates that polymeric nanoparticles and liposomes stand out as key tools for improving specific drug delivery to the site of action. In addition, solid lipid nanoparticles, squalene nanoparticles and nanobubbles have also been successfully proposed. Taken together, these strategies all offer many platforms for the design of nanocarriers that are suitable for future clinical translation.