Статті в журналах: "Drug delivery micellar systems"

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Demchuk, Zoriana, Mariya Savka, Andriy Voronov, Olga Budishevska, Volodymyr Donchak, and Stanislav Voronov. "Amphiphilic Polymers Containing Cholesterol for Drug Delivery Systems." Chemistry & Chemical Technology 10, no. 4s (December 25, 2016): 561–70. http://dx.doi.org/10.23939/chcht10.04si.561.

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The interaction of binary copolymers poly(maleic anhydride-co-poly(ethylene glycol) methyl ether methacrylate) with cholesterol results in formation of cholesterol containing polymers, which contain from 4.6 to 46.0 mol % monocholesteryl maleic links. Their structure was confirmed using functional analysis and IR spectroscopy. Acidic and anhydride links of these copolymers form polymeric salts if react with alkali. These salts are surfactants which in aqueous medium form a hierarchy micelles and micellar aggregates depending on the copolymer concentration. Using conductometry it was found that preferably monomolecular micelles are formed in dilute solutions, and micellar aggregates begin to form at higher concentrations. In aqueous media polymeric salts are able to solubilize such lipophilic substances as Sudan III dye and anticancer drug curcumin. Efficiency of solubilization towards Sudan III grows if the content of monocholesteryl maleic fragment in surfactant increases.

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Majumder, Nairrita, Nandita G Das, and Sudip K. Das. "Polymeric micelles for anticancer drug delivery." Therapeutic Delivery 11, no. 10 (October 2020): 613–35. http://dx.doi.org/10.4155/tde-2020-0008.

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Polymeric micelles have gained interest as novel drug delivery systems for the treatment and diagnosis of cancer, as they offer several advantages over conventional drug therapies. This includes drug targeting to tumor tissue, in vivo biocompatibility and biodegradability, prolonged circulation time, enhanced accumulation, retention of the drug loaded micelle in the tumor and decreased side effects. This article provides an overview on the current state of micellar formulations as nanocarriers for anticancer drugs and their effectiveness in cancer therapeutics, including their clinical status. The type of copolymers used, their physicochemical properties and characterization as well as recent developments in the design of functional polymeric micelles are highlighted. The article also presents the design and outcomes of various types of stimuli-responsive polymeric micelles.

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Tănase, Maria Antonia, Adina Raducan, Petruţa Oancea, Lia Mara Diţu, Miruna Stan, Cristian Petcu, Cristina Scomoroşcenco, Claudia Mihaela Ninciuleanu, Cristina Lavinia Nistor, and Ludmila Otilia Cinteza. "Mixed Pluronic—Cremophor Polymeric Micelles as Nanocarriers for Poorly Soluble Antibiotics—The Influence on the Antibacterial Activity." Pharmaceutics 13, no. 4 (March 24, 2021): 435. http://dx.doi.org/10.3390/pharmaceutics13040435.

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In this work, novel polymeric mixed micelles from Pluronic F127 and Cremophor EL were investigated as drug delivery systems for Norfloxacin as model antibiotic drug. The optimal molar ratio of surfactants was determined, in order to decrease critical micellar concentration (CMC) and prepare carriers with minimal surfactant concentrations. The particle size, zeta potential, and encapsulation efficiency were determined for both pure and mixed micelles with selected composition. In vitro release kinetics of Norfloxacin from micelles show that the composition of surfactant mixture generates tunable extended release. The mixed micelles exhibit good biocompatibility against normal fibroblasts MRC-5 cells, while some cytotoxicity was found in all micellar systems at high concentrations. The influence of the surfactant components in the carrier on the antibacterial properties of Norfloxacin was investigated. The drug loaded mixed micellar formulation exhibit good activity against clinical isolated strains, compared with the CLSI recommended standard strains (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922). P. aeruginosa 5399 clinical strain shows low sensitivity to Norfloxacin in all tested micelle systems. The results suggest that Cremophor EL-Pluronic F127 mixed micelles can be considered as novel controlled release delivery systems for hydrophobic antimicrobial drugs.

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Kim, Kyoung Nan, Keun Sang Oh, Jiwook Shim, Isabel R. Schlaepfer, Sana D. Karam, and Jung-Jae Lee. "Light-Responsive Polymeric Micellar Nanoparticles with Enhanced Formulation Stability." Polymers 13, no. 3 (January 26, 2021): 377. http://dx.doi.org/10.3390/polym13030377.

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Light-sensitive polymeric micelles have recently emerged as promising drug delivery systems for spatiotemporally controlled release of payload at target sites. Here, we developed diazonaphthoquinone (DNQ)-conjugated micellar nanoparticles that showed a change in polarity of the micellar core from hydrophobic to hydrophilic under UV light, releasing the encapsulated anti-cancer drug, doxetaxel (DTX). The micelles exhibited a low critical micelle concentration and high stability in the presence of bovine serum albumin (BSA) solution due to the hydrophobic and π–π stacking interactions in the micellar core. Cell studies showed enhanced cytotoxicity of DTX-loaded micellar nanoparticles upon irradiation. The enhanced stability would increase the circulation time of the micellar nanoparticles in blood, and enhance the therapeutic effectiveness for cancer therapy.

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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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Atanase, Leonard Ionut. "Micellar Drug Delivery Systems Based on Natural Biopolymers." Polymers 13, no. 3 (February 2, 2021): 477. http://dx.doi.org/10.3390/polym13030477.

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The broad diversity of structures and the presence of numerous functional groups available for chemical modifications represent an enormous advantage for the development of safe, non-toxic, and cost-effective micellar drug delivery systems (DDS) based on natural biopolymers, such as polysaccharides, proteins, and peptides. Different drug-loading methods are used for the preparation of these micellar systems, but it appeared that dialysis is generally recommended, as it avoids the formation of large micellar aggregates. Moreover, the preparation method has an important influence on micellar size, morphology, and drug loading efficiency. The small size allows the passive accumulation of these micellar systems via the permeability and retention effect. Natural biopolymer-based micellar DDS are high-value biomaterials characterized by good compatibility, biodegradability, long blood circulation time, non-toxicity, non-immunogenicity, and high drug loading, and they are biodegraded to non-toxic products that are easily assimilated by the human body. Even if some recent studies reported better antitumoral effects for the micellar DDS based on polysaccharides than for commercial formulations, their clinical use is not yet generalized. This review is focused on the studies from the last decade concerning the preparation as well as the colloidal and biological characterization of micellar DDS based on natural biopolymers.

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Pooja Mallya, Gowda D V, Mahendran B, Bhavya M V, and Vikas Jain. "Recent developments in nano micelles as drug delivery system." International Journal of Research in Pharmaceutical Sciences 11, no. 1 (January 7, 2020): 176–84. http://dx.doi.org/10.26452/ijrps.v11i1.1804.

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Targeting of the drug directly to the cells, tissues, or organs with no impact on healthy cells is a challenge. In the current era, it's been made possible by therapeutic interventions. The novel drug delivery systems such as nano particulates, liposomes, aquasomes, phytosomes, dendrimers, nano sponges, nano micelles are developed. Nano micelles are developed for efficient targeting and are currently in trend as therapeutic carriers of water-insoluble drugs. Micelles are self-assembling Nano-sized colloidal particles with a hydrophobic core and hydrophilic shell. Among the micelle-forming compounds, amphiphilic copolymers, i.e., polymers consisting of hydrophobic block and hydrophilic block, are gaining increasing attention. Polymeric micelles possess high stability both in vitro and in vivo with good biocompatibility. Nano micelles are used widely because of the smaller size range of 10 to 100nm, with greater drug loading capacity. Advantages over other dosage forms include solubilization of poorly soluble drugs, sustained release, protection of drugs from degradation and metabolism. The property discussed includes CMC, size, and aggregation number, and stability. CMC is the minimum polymer concentration required for micelle formation. Aggregation number (Nₐ) is the number of polymeric chains required to form micelles, and it ranges between tens to hundreds. Thermodynamic stability is based on size, the optical clarity of solution, viscosity, and surface tension. Kinetic stability accounts for micellar integrity. This review will discuss some recent trends in using micelles as pharmaceutical carriers such as to deliver drugs in conditions such as TB, cancer, ocular complications, etc.

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Wang, Jing, Xueqing Xing, Xiaocui Fang, Chang Zhou, Feng Huang, Zhonghua Wu, Jizhong Lou, and Wei Liang. "Cationic amphiphilic drugs self-assemble to the core–shell interface of PEGylated phospholipid micelles and stabilize micellar structure." Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 371, no. 2000 (October 13, 2013): 20120309. http://dx.doi.org/10.1098/rsta.2012.0309.

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Since polymeric micelles are promising and have potential in drug delivery systems, people have become more interested in studying the compatibility of polymeric carriers and drugs, which might help them to simplify the preparation method and increase the micellar stability. In this article, we report that cationic amphiphilic drugs can be easily encapsulated into PEGylated phospholipid (PEG–PE) micelles by self-assembly method and that they show high encapsulation efficiency, controllable drug release and better micellar stability than empty micelles. The representative drugs are doxorubicin and vinorelbine. However, gemcitabine and topotecan are not suitable for PEG–PE micelles due to lack of positive charge or hydrophobicity. Using a series of experiments and molecular modelling, we figured out the assembly mechanism, structure and stability of drug-loaded micelles, and the location of drugs in micelles. Integrating the above information, we explain the effect of the predominant force between drugs and polymers on the assembly mechanism and drug release behaviour. Furthermore, we discuss the importance of p K a and to evaluate the compatibility of drugs with PEG–PE in self-assembly preparation method. In summary, this work provides a scientific understanding for the reasonable designing of PEG–PE micelle-based drug encapsulation and might enlighten the future study on drug–polymer compatibility for other polymeric micelles.

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9

O'driscoll, Caitriona. "Micellar systems for oral drug delivery." Journal of Pharmacy and Pharmacology 50, S9 (September 1998): 13. http://dx.doi.org/10.1111/j.2042-7158.1998.tb02213.x.

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Biswas, Swati. "Polymeric micelles as drug-delivery systems in cancer: challenges and opportunities." Nanomedicine 16, no. 18 (August 2021): 1541–44. http://dx.doi.org/10.2217/nnm-2021-0081.

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Tweetable abstract Micelles are nanocarriers for hydrophobic chemotherapeutic drugs. This editorial discusses the current status of preclinical micellar research and sheds light on the possibility of their clinical translation.

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Hussein A. Abdul Hussein and Nidhal K. Maraie. "Highlights on polymeric micelles as versatile nanocarriers for drug transporting." Al Mustansiriyah Journal of Pharmaceutical Sciences 21, no. 2 (April 19, 2022): 21–30. http://dx.doi.org/10.32947/ajps.v21i2.806.

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Polymeric micelles are nanoscale core-shell structures formed by amphiphilic (block or graft) copolymers, that can self-aggregate in an aqueous medium. PMs characterized by small size, spherical shape, lower critical micellar concentration, which gave higher stability for PMs over conventional surfactant micelles. The core/shell structure permits polymeric micelle to entrap poor soluble drugs and can improve their solubility and permeability. The preparation of PMs tends to be relatively easy as compared to other novel drug delivery systems. This review focus on the general properties, types, types of copolymer utilized, formation mechanism, preparation methods, characterization techniques, and the applications on PMs.

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Valdivia, Victoria, Raúl Gimeno-Ferrero, Manuel Pernia Leal, Chiara Paggiaro, Ana María Fernández-Romero, María Luisa González-Rodríguez, and Inmaculada Fernández. "Biologically Relevant Micellar Nanocarrier Systems for Drug Encapsulation and Functionalization of Metallic Nanoparticles." Nanomaterials 12, no. 10 (May 20, 2022): 1753. http://dx.doi.org/10.3390/nano12101753.

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The preparation of new and functional nanostructures has received more attention in the scientific community in the past decade due to their wide application versatility. Among these nanostructures, micelles appear to be one of the most interesting supramolecular organizations for biomedical applications because of their ease of synthesis and reproducibility and their biocompatibility since they present an organization similar to the cell membrane. In this work, we developed micellar nanocarrier systems from surfactant molecules derived from oleic acid and tetraethylene glycol that were able to encapsulate and in vitro release the drug dexamethasone. In addition, the designed micelle precursors were able to functionalize metallic NPs, such as gold NPs and iron oxide NPs, resulting in monodispersed hybrid nanomaterials with high stability in aqueous media. Therefore, a new triazole-derived micelle precursor was developed as a versatile encapsulation system, opening the way for the preparation of new micellar nanocarrier platforms for drug delivery, magnetic resonance imaging, or computed tomography contrast agents for therapeutic and diagnostic applications.

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Gillies, E. R., and J. M. J. Fréchet. "Development of acid-sensitive copolymer micelles for drug delivery." Pure and Applied Chemistry 76, no. 7-8 (January 1, 2004): 1295–307. http://dx.doi.org/10.1351/pac200476071295.

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In recent years, supramolecular micellar assemblies formed from amphiphilic block copolymers have been receiving attention as potential drug carriers. The size of the carriers is ideal for avoiding rapid renal exclusion and reticuloendothelial uptake, and enables them to be targeted to certain tissues such as tumors. One important issue determining the effectiveness of a micellar drug carrier is the ability to control the time over which drug release takes place, or to possibly trigger drug release at a specific location or time. The mildly acidic pH encountered in tumor and inflammatory tissues as well as in the endosomal and lysosomal compartments of cells has inspired the development of micellar carriers capable of releasing their drug load in response to small changes in pH. One approach to the development of these systems has been to incorporate “titratable” groups such as amines and carboxylic acids into the copolymer backbone, thus altering the solubility of the polymer upon protonation and disrupting micelle formation. Another approach has been to incorporate acid-degradable linkages into the copolymer, either for direct attachment of the drug, or to cause a structural change of such magnitude that micellar integrity is lost and the drug is released.

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da Silva Souza Campanholi, Katieli, Flávia Amanda Pedroso de Morais, Évelin Lemos de Oliveira, Maycon Renan Santos Lima, Elza Aparecida da Silva, Expedito Leite Silva, and Wilker Caetano. "INTERAÇÃO DO LAPACHOL COM NANOPLATAFORMAS MICELARES DRUG DELIVERY." COLLOQUIUM EXACTARUM 13, no. 1 (April 28, 2021): 09–18. http://dx.doi.org/10.5747/ce.2021.v13.n1.e345.

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The high toxicity of several systemically administered drugs is due to low specificity to diseased cells. This results in adverse effects and discomfort to patients. A promising strategy to enhance the therapeutic efficacy and clinical use of activeingredients is their incorporation into nanostructured micellar systems. These nanocarriers are widely addressed in the literature as drug delivery systems. Thus, this paper discusses aspects related to the interaction capacity of the natural drug lapachol with two micellar systems (F127 and P123), aiming to obtain a new drug for systemic administration. For this, previous studies were conducted to evaluate the variations that the aggregation of lapachol results in its spectral behavior. Subsequently, the interaction of lapachol with drug delivery systems was investigated by monitoring the fluorescence emission spectra of the drug. In general, the results obtained were promising and enrich the current therapeutic arsenal with a new medicine proposal, whose drug has established ethnopharmacological and scientific recognition.

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Supraja, Bommala, and Saritha Mulangi. "An updated review on pharmacosomes, a vesicular drug delivery system." Journal of Drug Delivery and Therapeutics 9, no. 1-s (February 15, 2019): 393–402. http://dx.doi.org/10.22270/jddt.v9i1-s.2234.

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Novel drug delivery system mainly consents about achieving the targeted concentration to release the drug at targeted site by using carrier system, altering the structure and microenvironment around the drug. Especially drugs which are having narrow therapeutic window are difficult to formulate, with the advantage of novel drug delivery systems like particulate, polymeric carrier, macromolecular and cellular carriers. They are used to reduce complications as well as release the drug in a determined fusion at targeted site. In vesicular drug delivery system drug binds covalently to the lipid molecule by which the drug release is in a controlled manner and also drugs which are of hydrophilic or lipophilic nature can be delivered by using vesicular drug delivery systems. The release of drug from the vesicles depends on the physicochemical properties of both the drug and carrier. Vesicular drug delivery includes liposomes, niososmes, transferosomes, pharmacosomes, electrosomes, ethosomes etc. Of all these drug delivery systems pharmacosomes are having more advantages like no leakage or loss of drug, stability, high entrapment efficiency etc, pharmacosomes may be hexagonal aggregates , ultrafine vesicular and micellar forms. Both synthetic and natural drugs which are facing difficulties like low solubility and low permeability can be effectively formulated and can achieve required pharmacokinetic and pharmacodynamic parameters. Pharmacosomes are prepared by hand shaking method, ether injection, solvent evaporation method, anhydrous co-solvent lyophilyzation, supercritical fluid approach and other alternative methods they are characterized by complex determination, surface morphology, drug entrapment, solubility, drug lipid compatibility, crystal state measurement, dissolution studies and in vitro drug release rate. Keywords: Pharmacosomes, covalently, vesicular drug delivery system, hexagonal aggregates, micellar, ultrafine.

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Popovici, Corina, Marcel Popa, Valeriu Sunel, Leonard Ionut Atanase, and Daniela Luminita Ichim. "Drug Delivery Systems Based on Pluronic Micelles with Antimicrobial Activity." Polymers 14, no. 15 (July 25, 2022): 3007. http://dx.doi.org/10.3390/polym14153007.

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Bacterial oral diseases are chronic, and, therefore, require appropriate treatment, which involves various forms of administration and dosing of the drug. However, multimicrobial resistance is an increasing issue, which affects the global health system. In the present study, a commercial amphiphilic copolymer, Pluronic F127, was used for the encapsulation of 1-(5′-nitrobenzimidazole-2′-yl-sulphonyl-acetyl)-4-aryl-thiosemicarbazide, which is an original active pharmaceutical ingredient (API) previously synthesized and characterized by our group, at different copolymer/API weight ratios. The obtained micellar systems, with sizes around 20 nm, were stable during 30 days of storage at 4 °C, without a major increase of the Z-average sizes. As expected, the drug encapsulation and loading efficiencies varied with the copolymer/API ratio, the highest values of 84.8 and 11.1%, respectively being determined for the F127/API = 10/1 ratio. Moreover, in vitro biological tests have demonstrated that the obtained polymeric micelles (PMs) are both hemocompatible and cytocompatible. Furthermore, enhanced inhibition zones of 36 and 20 mm were observed for the sample F127/API = 2/1 against S. aureus and E. coli, respectively. Based on these encouraging results, it can be admitted that these micellar systems can be an efficient alternative for the treatment of bacterial oral diseases, being suitable either by injection or by a topical administration.

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Sutton, Damon, Norased Nasongkla, Elvin Blanco, and Jinming Gao. "Functionalized Micellar Systems for Cancer Targeted Drug Delivery." Pharmaceutical Research 24, no. 6 (March 24, 2007): 1029–46. http://dx.doi.org/10.1007/s11095-006-9223-y.

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Galdopórpora, Juan M., Camila Martinena, Ezequiel Bernabeu, Jennifer Riedel, Lucia Palmas, Ines Castangia, Maria Letizia Manca, et al. "Inhalable Mannosylated Rifampicin–Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy." Pharmaceutics 14, no. 5 (April 28, 2022): 959. http://dx.doi.org/10.3390/pharmaceutics14050959.

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Among respiratory infections, tuberculosis was the second deadliest infectious disease in 2020 behind COVID-19. Inhalable nanocarriers offer the possibility of actively targeting anti-tuberculosis drugs to the lungs, especially to alveolar macrophages (cellular reservoirs of the Mycobacterium tuberculosis). Our strategy was based on the development of a mannose-decorated micellar nanoformulation based in Soluplus® to co-encapsulate rifampicin and curcumin. The former is one of the most effective anti-tuberculosis first-line drugs, while curcumin has demonstrated potential anti-mycobacterial properties. Mannose-coated rifampicin (10 mg/mL)–curcumin (5 mg/mL)-loaded polymeric micelles (10% w/v) demonstrated excellent colloidal properties with micellar size ~108 ± 1 nm after freeze-drying, and they remain stable under dilution in simulated interstitial lung fluid. Drug-loaded polymeric micelles were suitable for drug delivery to the deep lung with lung accumulation, according to the in vitro nebulization studies and the in vivo biodistribution assays of radiolabeled (99mTc) polymeric micelles, respectively. Hence, the nanoformulation did not exhibit hemolytic potential. Interestingly, the addition of mannose significantly improved (5.2-fold) the microbicidal efficacy against Mycobacterium tuberculosis H37Rv of the drug-co-loaded systems in comparison with their counterpart mannose-free polymeric micelles. Thus, this novel inhaled nanoformulation has demonstrated its potential for active drug delivery in pulmonary tuberculosis therapy.

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Paraiso, West Kristian D., Jesús García Chica, Xavier Ariza, Jordi García, Kazunori Kataoka, Rosalía Rodríguez Rodríguez, and Sabina Quader. "A New Nanomedicine Platform to Deliver a Carnitine Palmitoyl-Transferase 1 (CPT1) Inhibitor into Glioma Cells and Neurons." Materials Proceedings 4, no. 1 (November 12, 2020): 58. http://dx.doi.org/10.3390/iocn2020-07986.

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Obesity and glioblastoma multiforme (GB) are two unmet medical needs where effective therapies are lacking. Carnitine palmitoyl transferase 1 (CPT1), an enzyme catalyzing the rate-limiting step in fatty acid oxidation (FAO), is a viable target for both diseases. C75, a fatty acid synthase (FAS) inhibitor, forms an adduct with coenzyme A (CoA) to form C75-CoA, which is a strong competitive inhibitor to CPT1 that is selective in its target. However, it is polar and charged, having low cell membrane permeability, and therefore needing a delivery system for intracellular transport. (±)-C75-CoA and its enantio-separated forms (+)- and (−)-C75-CoA were used to form poly-ion complex (PIC) micelles with the cationic block co-polymer PEG-PAsp(DET). The drug and polymer were mixed in a 1:1 anion/cation ratio to give 50–70 nm micelles with a unimodal size profile and narrow polydispersity. Size was maintained upon introduction of physiological saline. Micellar (±)-, (+)-, and (−)-C75-CoA were all significantly more cytotoxic compared to the respective free drugs in U87MG. We examined whether C75-CoA inhibits FAO by measuring ATP concentrations in U87MG and GT1-7. ATP generation was found to be hampered after adding C75-CoA in both cell types, with micelle-treated cells producing significantly lower ATP than those treated with free drug, suggesting that the effective intracellular delivery of C75-CoA leads to a more pronounced FAO inhibition. A fluorescent CoA derivative, Fluor-CoA, also yielded monodisperse micelles similar to C75-CoA. Micellar internalization was significantly greater than that of the free dye. Uptake of both increased with time, with this effect is more pronounced in U87MG than GT1-7. The %Fluor-CoA+ cells were also expressively higher for the micelle across cell lines. From this data, it can be convincingly concluded that neuronal and glioma cellular uptake of micelles is superior to that of the free dye, validating the need for cellular delivery systems for anionic, CoA-type molecules. The micellar form neutralized the negative charge of the cargo, promoting transport into the cell. These outcomes strongly support the effectiveness of using a PIC micelle-type system to deliver anionic small molecules into glioma cells and neurons meant to inhibit enzymes such as CPT1, for future applications in diseases like obesity and cancer.

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Mandracchia, Delia, Adriana Trapani, Sara Perteghella, Cinzia Di Franco, Maria Torre, Enrica Calleri, and Giuseppe Tripodo. "A Micellar-Hydrogel Nanogrid from a UV Crosslinked Inulin Derivative for the Simultaneous Delivery of Hydrophobic and Hydrophilic Drugs." Pharmaceutics 10, no. 3 (July 19, 2018): 97. http://dx.doi.org/10.3390/pharmaceutics10030097.

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Hydrogels are among the most common materials used in drug delivery, as polymeric micelles are too. They, preferentially, load hydrophilic and hydrophobic drugs, respectively. In this paper, we thought to combine the favorable behaviors of both hydrogels and polymeric micelles with the specific aim of delivering hydrophilic and hydrophobic drugs for dual delivery in combination therapy, in particular for colon drug delivery. Thus, we developed a hydrogel by UV crosslinking of a methacrylated (MA) amphiphilic derivative from inulin (INU) (as known INU is specifically degraded into the colon) and vitamin E (VITE), called INVITEMA. The methacrylated micelles were physicochemically characterized and subjected to UV irradiation to form what we called the “nanogrids”. The INVITEMA nanogrids were characterized by DSC, SEM, TEM, water uptake and beclomethasone dipropionate (BDP) release. In particular, the release of the hydrophobic drug was specifically assessed to verify that it can spread along the hydrophilic portions and, therefore, effectively released. These systems can open new pharmaceutical applications for known hydrogels or micelle systems, considering that in literature only few examples are present.

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Tawfik, Salah M., Shavkatjon Azizov, Mohamed R. Elmasry, Mirkomil Sharipov, and Yong-Ill Lee. "Recent Advances in Nanomicelles Delivery Systems." Nanomaterials 11, no. 1 (December 30, 2020): 70. http://dx.doi.org/10.3390/nano11010070.

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The efficient and selective delivery of therapeutic drugs to the target site remains the main obstacle in the development of new drugs and therapeutic interventions. Up until today, nanomicelles have shown their prospective as nanocarriers for drug delivery owing to their small size, good biocompatibility, and capacity to effectively entrap lipophilic drugs in their core. Nanomicelles are formed via self-assembly in aqueous media of amphiphilic molecules into well-organized supramolecular structures. Molecular weights and structure of the core and corona forming blocks are important properties that will determine the size of nanomicelles and their shape. Selective delivery is achieved via novel design of various stimuli-responsive nanomicelles that release drugs based on endogenous or exogenous stimulations such as pH, temperature, ultrasound, light, redox potential, and others. This review summarizes the emerging micellar nanocarriers developed with various designs, their outstanding properties, and underlying principles that grant targeted and continuous drug delivery. Finally, future perspectives, and challenges for nanomicelles are discussed based on the current achievements and remaining issues.

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Shahriari, Mahsa, Vladimir P. Torchilin, Seyed Mohammad Taghdisi, Khalil Abnous, Mohammad Ramezani, and Mona Alibolandi. "“Smart” self-assembled structures: toward intelligent dual responsive drug delivery systems." Biomaterials Science 8, no. 21 (2020): 5787–803. http://dx.doi.org/10.1039/d0bm01283a.

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In the current review, we summarized the polymer and peptide-based schizophrenic copolymers which could form micellar and vesicular (polymersome) systems providing novel structures with beneficial applications.

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Kunitskaya, L., and T. Zheltonozhskaya. "BEHAVIOR OF ACID HYDROLYSIS IN BLOCK COPOLYMERS COMPRISING POLYACRYLAMIDE AND POLY(ETHYLENE OXIDE)." Bulletin of Taras Shevchenko National University of Kyiv. Chemistry, no. 1(55) (2018): 60–63. http://dx.doi.org/10.17721/1728-2209.2018.1(55).15.

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Polymeric micelles self-assembled from amphiphilic block copolymers have been intensively investigated as nano-carrier systems for tumor-targeted drug delivery. Diblock copolymers PEO-b-PAAm (DBC) and thriblock copolymers PAAm-b-PEO-b-PAAm (TBC) contained biocompatible chemically complementary polyacrylamide and poly(ethylene oxide) formed micellar structures in aqueous solutions which have hydrophobic complex “core” formed by the hydrogen-bonded PEO/PAAm chains and hydrophilic “corona” of the surplus segments of PAAm blocks. The ability of DBCs and TBCs to bind the anticancer drug doxorubicin was established. This opened the new prospects for using such copolymers as nanocontainers for toxic and poorly soluble drugs. Successful implementation of DBC and TBC micelles for drug delivery requires the presence a special vectors, particularly galactose, in the micellar “corona”. Such vectors can recognize corresponding receptors on a cellular surface, interact with them, and penetrate into the intracellular space by the endocytosis pathway. In order to introduce the galactose vectors into DBC or TBC micelles, the corona forming PAA blocks have to contain the corresponding active groups, such as –OH, –COO–, –NH2. Therefore, the methods of DBCs (TBCs) functionalization are particularly important since it allows to input the necessary saccharides and also to expand the applications of micellar nanocarriers to encapsulate and delivery of both the drug substances and genetic materials. In the present work, the polymer-analogous conversion of DBCs and TBCs by the acid hydrolysis of PAAm blocks at 50°C was studied. Kinetic investigations of the hydrolysis reaction of DBCs (TBCs) in comparison with pure PAAm were performed by potentiometric titration. It was established that the process of acid hydrolysis of diblock- and thriblock copolymers depends on the blocks length and occurs more intensive in the block copolymers which have longest PEO and PAA chains. The reasons for this phenomenon are discussed. The fact is that hydrolysis of DBCs samples develops efficiently in comparison with TBCs ones attributed to the steric obstacles which appears in TBCs micelles because of their more complicated structure.

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Berillo, Dmitriy, Adilkhan Yeskendir, Zharylkasyn Zharkinbekov, Kamila Raziyeva, and Arman Saparov. "Peptide-Based Drug Delivery Systems." Medicina 57, no. 11 (November 5, 2021): 1209. http://dx.doi.org/10.3390/medicina57111209.

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Peptide-based drug delivery systems have many advantages when compared to synthetic systems in that they have better biocompatibility, biochemical and biophysical properties, lack of toxicity, controlled molecular weight via solid phase synthesis and purification. Lysosomes, solid lipid nanoparticles, dendrimers, polymeric micelles can be applied by intravenous administration, however they are of artificial nature and thus may induce side effects and possess lack of ability to penetrate the blood-brain barrier. An analysis of nontoxic drug delivery systems and an establishment of prospective trends in the development of drug delivery systems was needed. This review paper summarizes data, mainly from the past 5 years, devoted to the use of peptide-based carriers for delivery of various toxic drugs, mostly anticancer or drugs with limiting bioavailability. Peptide-based drug delivery platforms are utilized as peptide–drug conjugates, injectable biodegradable particles and depots for delivering small molecule pharmaceutical substances (500 Da) and therapeutic proteins. Controlled drug delivery systems that can effectively deliver anticancer and peptide-based drugs leading to accelerated recovery without significant side effects are discussed. Moreover, cell penetrating peptides and their molecular mechanisms as targeting peptides, as well as stimuli responsive (enzyme-responsive and pH-responsive) peptides and peptide-based self-assembly scaffolds are also reviewed.

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Zilinskas, Gregory J., Abdolrasoul Soleimani, and Elizabeth R. Gillies. "Poly(ester amide)-Poly(ethylene oxide) Graft Copolymers: Towards Micellar Drug Delivery Vehicles." International Journal of Polymer Science 2012 (2012): 1–11. http://dx.doi.org/10.1155/2012/564348.

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Micelles formed from amphiphilic copolymers are promising materials for the delivery of drug molecules, potentially leading to enhanced biological properties and efficacy. In this work, new poly(ester amide)-poly(ethylene oxide) (PEA-PEO) graft copolymers were synthesized and their assembly into micelles in aqueous solution was investigated. It was possible to tune the sizes of the micelles by varying the PEO content of the polymers and the method of micelle preparation. Under optimized conditions, it was possible to obtain micelles with diameters less than 100 nm as measured by dynamic light scattering and transmission electron microscopy. These micelles were demonstrated to encapsulate and release a model drug, Nile Red, and were nontoxic to HeLa cells as measured by an MTT assay. Overall, the properties of these micelles suggest that they are promising new materials for drug delivery systems.

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Naqvi, Andleeb Z., Sahar Noori, and Kabir-ud-Din Kabir-ud-Din. "Mixed micellization of dimeric surfactant–amphiphilic drug systems: effect of surfactant structure." RSC Advances 6, no. 24 (2016): 20324–36. http://dx.doi.org/10.1039/c5ra24058a.

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For their applications as drug delivery vehicles, the mixed interfacial/micellar behaviour of zwitterionic, cocogem and anionic dimeric surfactants with an amphiphilic drug imipramine hydrochloride in aqueous solutions has been investigated.

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27

Neugebauer, Dorota, Justyna Odrobińska, Rafał Bielas, and Anna Mielańczyk. "Design of systems based on 4-armed star-shaped polyacids for indomethacin delivery." New Journal of Chemistry 40, no. 12 (2016): 10002–11. http://dx.doi.org/10.1039/c6nj02346k.

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Iurciuc-Tincu, Camelia-Elena, Monica Stamate Cretan, Violeta Purcar, Marcel Popa, Oana Maria Daraba, Leonard Ionut Atanase, and Lacramioara Ochiuz. "Drug Delivery System Based on pH-Sensitive Biocompatible Poly(2-vinyl pyridine)-b-poly(ethylene oxide) Nanomicelles Loaded with Curcumin and 5-Fluorouracil." Polymers 12, no. 7 (June 28, 2020): 1450. http://dx.doi.org/10.3390/polym12071450.

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Smart polymeric micelles (PMs) are of practical interest as nanocarriers for the encapsulation and controlled release of hydrophobic drugs. Two hydrophobic drugs, naturally-based curcumin (Cur) and synthetic 5-fluorouracil (5-FU), were loaded into the PMs formed by a well-defined pH-sensitive poly(2-vinyl pyridine)-b-poly(ethylene oxide) (P2VP90-b-PEO398) block copolymer. The influence of the drug loading on the micellar sizes was investigated by dynamic light scattering (DLS) and it appears that the size of the PMs increases from around 60 to 100 nm when Cur is loaded. On the contrary, the loading of the 5-FU has a smaller effect on the micellar sizes. This difference can be attributed to higher molar mass of Cur with respect to 5-FU but also to higher loading efficiency of Cur, 6.4%, compared to that of 5-FU, 5.8%. In vitro drug release was studied at pH 2, 6.8, and 7.4, and it was observed that the pH controls the release of both drugs. At pH 2, where the P2VP sequences from the “frozen-in” micellar core are protonated, the drug release efficiencies exceed 90%. Moreover, it was demonstrated, by in vitro assays, that these PMs are hemocompatible and biocompatible. Furthermore, the PMs protect the Cur against the photo-degradation, whereas the non-ionic PEO corona limits the adsorption of bovine serum albumin (BSA) protein on the surface. This study demonstrates that these pH-sensitive PMs are suitable for practical utilization as human-safe and smart, injectable drug delivery systems.

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Lather, V., V. Saini, and D. Pandita. "Polymeric Micelles of Modified Chitosan Block Copolymer as Nanocarrier for Delivery of Paclitaxel." Current Nanomedicine 9, no. 1 (March 15, 2019): 86–96. http://dx.doi.org/10.2174/2468187308666180426120050.

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Background: Polymeric micelles are being used as successful nanocarriers for the delivery of diverse drug molecules due to properties like solubilization, selective targeting, P-glycoprotein inhibition, altered drug internalization route and subcellular localization etc. Objective: The present investigation was planned to prepare and characterize novel polymeric micelles derived from self assembly of amphiphilic chitosan-bile salt derivative (CS-mPEG-DA) as nanocarrier and evaluate their potential in delivery of an anticancer drug, paclitaxel. Method: Paclitaxel, a diterpenoid compound, useful in clinical treatment of several solid tumors such as ovarian cancer, breast cancer and lung cancer suffers from limitations like low aqueous solubility and bioavailability and subsequently was used as the model drug. Results: Paclitaxel was successfully incorporated into polymeric micelles using dialysis and emulsion method with encapsulation efficiency up to 95% having particle size in nanometer range (<200 nm). Paclitaxel loaded micelles were found to release the drug in a sustained manner up to 96 h in PBS containing 0.1% (w/v) tween 80 at 37°C. The micelles powders subjected to stability studies for a period of 90 days were found to be stable at 4 ± 2°C with respect to particle size and drug content. In vivo cytotoxicity assay confirmed that paclitaxel encapsulated in polymeric micelles showed higher cytotoxicity against cultured MCF-7 breast cancer cells than paclitaxel alone. Conclusion: Polymeric micellar systems derived from copolymerization of chitosan exhibit a great potential in successful delivery of poorly water soluble or low bioavailable drugs like paclitaxel.

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Jain, Shikha, Vikas Jain, and S. C. Mahajan. "Lipid Based Vesicular Drug Delivery Systems." Advances in Pharmaceutics 2014 (September 2, 2014): 1–12. http://dx.doi.org/10.1155/2014/574673.

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Vesicular drug delivery system can be defined as highly ordered assemblies consisting of one or more concentric bilayers formed as a result of self-assembling of amphiphilic building blocks in presence of water. Vesicular drug delivery systems are particularly important for targeted delivery of drugs because of their ability to localize the activity of drug at the site or organ of action thereby lowering its concentration at the other sites in body. Vesicular drug delivery system sustains drug action at a predetermined rate, relatively constant (zero order kinetics), efficient drug level in the body, and simultaneously minimizes the undesirable side effects. It can also localize drug action in the diseased tissue or organ by targeted drug delivery using carriers or chemical derivatization. Different types of pharmaceutical carriers such as polymeric micelles, particulate systems, and macro- and micromolecules are presented in the form of novel drug delivery system for targeted delivery of drugs. Particulate type carrier also known as colloidal carrier system, includes lipid particles, micro- and nanoparticles, micro- and nanospheres, polymeric micelles and vesicular systems like liposomes, sphingosomes, niosomes, transfersomes, aquasomes, ufasomes, and so forth.

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Rodriguez-Perez, A. I., C. Rodriguez-Tenreiro, C. Alvarez-Lorenzo, A. Concheiro, and J. J. Torres-Labandeira. "Drug Solubilization and Delivery from Cyclodextrin-Pluronic Aggregates." Journal of Nanoscience and Nanotechnology 6, no. 9 (September 1, 2006): 3179–86. http://dx.doi.org/10.1166/jnn.2006.472.

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Colloidal systems based on Pluronic® F127 (PF127) and hydroxypropyl-beta-cyclodextrin (HPβCD) have been characterized with a view to their potential use as delivery systems of hydrophobic drugs. Complexation of PF127 and HPβCD was evaluated by surface tension measurements, 1H-NMR spectroscopy and transmission electron microscopy. The critical micellar concentration, CMC, at 25 °C of PF127 (0.39 mM in pH 5.8 and 7.4 phosphate buffers, and 0.59 mM in pH 4.5 acetic/acetate and lactic/lactate buffers) was shifted to higher values by the addition of 38.17 mM HP CD (CMCapp = 1.18 mM). This is related to the threading of HPβCD onto the PF127 chains, as confirmed by 1H NMR experiments. HPβCD at this concentration notably raised the sol–gel transition temperature; the minimum PF127 concentration required for providing gelling systems in physiological environments being 13.4 mM. Both HPβCD and PF127 by themselves are able to notably increase the solubility of sertaconazole (SN). At HPβCD concentrations below 80 mM, an additive effect of both components on SN solubility was observed. At greater HPβCD concentrations, a non-additive increase occurred, which is related to the complexation of some PF127 unimers with HPβCD molecules, decreasing the total number of micelles and HPβCD cavities available for interacting with SN. The 13.4 mM PF127/38.17 mM HPβCD system, able to increase up to 100 times the SN solubility in pH5.8 phosphate buffer, showed temperature-dependent drug diffusion coefficients, able to control the release for one week at 37 °C.

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Boddu, Sai H. S., Prakash Bhagav, Pradeep K. Karla, Shery Jacob, Mansi D. Adatiya, Tejas M. Dhameliya, Ketan M. Ranch, and Amit K. Tiwari. "Polyamide/Poly(Amino Acid) Polymers for Drug Delivery." Journal of Functional Biomaterials 12, no. 4 (October 8, 2021): 58. http://dx.doi.org/10.3390/jfb12040058.

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Polymers have always played a critical role in the development of novel drug delivery systems by providing the sustained, controlled and targeted release of both hydrophobic and hydrophilic drugs. Among the different polymers, polyamides or poly(amino acid)s exhibit distinct features such as good biocompatibility, slow degradability and flexible physicochemical modification. The degradation rates of poly(amino acid)s are influenced by the hydrophilicity of the amino acids that make up the polymer. Poly(amino acid)s are extensively used in the formulation of chemotherapeutics to achieve selective delivery for an appropriate duration of time in order to lessen the drug-related side effects and increase the anti-tumor efficacy. This review highlights various poly(amino acid) polymers used in drug delivery along with new developments in their utility. A thorough discussion on anticancer agents incorporated into poly(amino acid) micellar systems that are under clinical evaluation is included.

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Wang, Zhao, Xinyu Guo, Lingyun Hao, Xiaojuan Zhang, Qing Lin, and Ruilong Sheng. "Charge-Convertible and Reduction-Sensitive Cholesterol-Containing Amphiphilic Copolymers for Improved Doxorubicin Delivery." Materials 15, no. 18 (September 18, 2022): 6476. http://dx.doi.org/10.3390/ma15186476.

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For achieving successful chemotherapy against cancer, designing biocompatible drug delivery systems (DDSs) with long circulation times, high cellular endocytosis efficiency, and targeted drug release is of upmost importance. Herein, a well-defined PEG-b-P(MASSChol-co-MANBoc) block copolymer bearing redox-sensitive cholesteryl-side group was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization (with non-redox PEG-b-P(MACCChol-co-MAN-DCA) as the reference), and 1,2-dicarboxylic-cyclohexene acid (DCA) was then grafted onto the hydrophobic block to endow it with charge-convertible characteristics under a tumor microenvironment. The amphiphilic copolymer could be assembled into polymeric spherical micelles (SSMCs) with polyethylene glycol (PEG) as the corona/shell, and anti-cancer drug doxorubicin (DOX) was successfully encapsulated into the micellar core via strong hydrophobic and electrostatic interactions. This nanocarrier showed high stability in the physiological environment and demonstrated “smart” surface charge conversion from negative to positive in the slightly acidic environment of tumor tissues (pH 6.5~6.8), as determined by dynamic light scattering (DLS). Moreover, the cleavage of a disulfide bond linking the cholesterol grafts under an intracellular redox environment (10 mM GSH) resulted in micellar dissociation and accelerated drug release, with the non-redox-responsive micelles (CCMCs) as the control. Additionally, a cellular endocytosis and tumor proliferation inhibition study against MCF-7 tumor cells demonstrated the enhanced endocytosis and tumor cell inhibitory efficiency of dual-responsive SSMCs/DOX nanomedicines, revealing potentials as multifunctional nanoplatforms for effective oncology treatment.

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Garg, Unnati, Swati Chauhan, Upendra Nagaich, and Neha Jain. "Current Advances in Chitosan Nanoparticles Based Drug Delivery and Targeting." Advanced Pharmaceutical Bulletin 9, no. 2 (June 1, 2019): 195–204. http://dx.doi.org/10.15171/apb.2019.023.

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Nanoparticles (NPs) have been found to be potential targeted and controlled release drug delivery systems. Various drugs can be loaded in the NPs to achieve targeted delivery. Chitosan NPs being biodegradable, biocompatible, less toxic and easy to prepare, are an effective and potential tool for drug delivery. Chitosan is natural biopolymer which can be easily functionalized to obtain the desired targeted results and is also approved by GRAS (Generally Recognized as Safe by the United States Food and Drug Administration [US FDA]). Various methods for preparation of chitosan NPs include, ionic cross-linking, covalent cross-linking, reverse micellar method, precipitation and emulsion-droplet coalescence method. Chitosan NPs are found to have plethora of applications in drug delivery diagnosis and other biological applications. The key applications include ocular drug delivery, per-oral delivery, pulmonary drug delivery, nasal drug delivery, mucosal drug delivery, gene delivery, buccal drug delivery, vaccine delivery, vaginal drug delivery and cancer therapy. The present review describes the formation of chitosan, synthesis of chitosan NPs and their various applications in drug delivery.

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Zhao, Zekai, Ying Zhang, Chunli Tian, Tingjie Yin, and Can Zhang. "Facile dynamic one-step modular assembly based on boronic acid-diol for construction of a micellar drug delivery system." Biomaterials Science 6, no. 10 (2018): 2605–18. http://dx.doi.org/10.1039/c8bm00712h.

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36

Sumer Bolu, Burcu, Bianka Golba, Amitav Sanyal, and Rana Sanyal. "Trastuzumab targeted micellar delivery of docetaxel using dendron–polymer conjugates." Biomaterials Science 8, no. 9 (2020): 2600–2610. http://dx.doi.org/10.1039/c9bm01764j.

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Nicoud, Melisa B., Ignacio A. Ospital, Mónica A. Táquez Delgado, Jennifer Riedel, Pedro Fuentes, Ezequiel Bernabeu, Mara R. Rubinstein, et al. "Nanomicellar Formulations Loaded with Histamine and Paclitaxel as a New Strategy to Improve Chemotherapy for Breast Cancer." International Journal of Molecular Sciences 24, no. 4 (February 10, 2023): 3546. http://dx.doi.org/10.3390/ijms24043546.

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Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Currently, paclitaxel (PTX) represents the first-line therapy for TNBC; however it presents a hydrophobic behavior and produces severe adverse effects. The aim of this work is to improve the therapeutic index of PTX through the design and characterization of novel nanomicellar polymeric formulations composed of a biocompatible copolymer Soluplus® (S), surface-decorated with glucose (GS), and co-loaded either with histamine (HA, 5 mg/mL) and/or PTX (4 mg/mL). Their micellar size, evaluated by dynamic light scattering, showed a hydrodynamic diameter between 70 and 90 nm for loaded nanoformulations with a unimodal size distribution. Cytotoxicity and apoptosis assays were performed to assess their efficacy in vitro in human MDA-MB-231 and murine 4T1 TNBC cells rendering optimal antitumor efficacy in both cell lines for the nanoformulations with both drugs. In a model of TNBC developed in BALB/c mice with 4T1 cells, we found that all loaded micellar systems reduced tumor volume and that both HA and HA-PTX-loaded SG micelles reduced tumor weight and neovascularization compared with the empty micelles. We conclude that HA-PTX co-loaded micelles in addition to HA-loaded formulations present promising potential as nano-drug delivery systems for cancer chemotherapy.

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Niesyto, Katarzyna, Aleksy Mazur, and Dorota Neugebauer. "Dual-Drug Delivery via the Self-Assembled Conjugates of Choline-Functionalized Graft Copolymers." Materials 15, no. 13 (June 24, 2022): 4457. http://dx.doi.org/10.3390/ma15134457.

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Graft copolymers based on a choline ionic liquid (IL), [2-(methacryloyloxy)ethyl]-trimethylammonium chloride (TMAMA), were obtained by atom transfer radical polymerization. The presence of chloride counterions in the trimethylammonium groups promoted anion exchange to introduce fusidate anions (FUS, 32–55 mol.%) as the pharmaceutical anions. Both the choline-based IL copolymers and their ionic drug-carrier conjugates (FUS systems as the first type, 26–208 nm) formed micellar structures (CMC = 0.011–0.025 mg/mL). The amphiphilic systems were advantageous for the encapsulation of rifampicin (RIF, 40–67 mol.%), a well-known antibiotic, resulting in single-drug (RIF systems as the second type, 40–95 nm) and dual-drug systems (FUS/RIF as the third type, 31–65 nm). The obtained systems released significant amounts of drugs (FUS > RIF), which could be adjusted by the content of ionic units and the length of the copolymer side chains. The dual-drug systems released 31–55% FUS (4.3–5.6 μg/mL) and 19–31% RIF (3.3–4.0 μg/mL), and these results were slightly lower than those for the single-drug systems, reaching 45–81% for FUS (3.8–8.2 μg/mL) and 20–37% for RIF (3.4–4.0 μg/mL). The designed polymer systems show potential as co-delivery systems for combined therapy against drug-resistant strains using two drugs in one formula instead of the separate delivery of two drugs.

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Wenceslau, Adriana C., Guilherme L. Q. C. Ferreira, Noboru Hioka, and Wilker Caetano. "Spectroscopic studies of pyridil and methoxyphenyl porphyrins in homogeneous and Pluronic®-based nanostructured systems." Journal of Porphyrins and Phthalocyanines 19, no. 11 (November 2015): 1168–76. http://dx.doi.org/10.1142/s1088424615500996.

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Spectroscopic properties of Porphyrins TPyP (tetra(4-pyridil)porphyrin), TMPP (tetrakis(4-methoxypheny) porphyrin) and its zinc metaled derivatives porphyrins Zn-TPyP and Zn-TMPP respectively, were studied in homogeneous and micro heterogeneous systems, comprising nanostructured Pluronic® copolymeric micellar systems, as a promising drug delivery systems for the porphyrins investigated. Physico-chemical properties such as, hydrophobicity degree, self- aggregation in solvents of different polarities and water/ethanol mixtures (monofasic binary), as well as kinetics profile and isotherm binding, molecular organization, [Formula: see text] and relative localization in neutral micellar systems. The hydrophobic character was the key to relative drug location in the micellar systems. In homogenous solvents systems the porphyrins presented relatively high values of molar absorptivity and low values of [Formula: see text]. The K[Formula: see text] values obtained are modulated by the structure of porphyrins, state of aggregation, as well as, structure and macro molecular self-organization of copolymers. Fluorescence quenching studies have shown that porphyrins in F-127 are located in a less hydrophobic region than the porphyrins in P-123, which are located preferentially in a deeper micellar microenvironment. The zinc porphyrins showed high values of K[Formula: see text]. Thus, the association of the porphyrins with specific binding sites of micellar systems is strongly modulated by the presence of the metal coordinated to the porphyrinic ring.

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40

Namazi, Hassan, and Saeed Jafarirad. "Invitro Photo-Controlled Drug Release System Based on Amphiphilic Linear-Dendritic Diblock Copolymers; Self-Assembly Behavior and Application as Nanocarrier." Journal of Pharmacy & Pharmaceutical Sciences 14, no. 2 (May 8, 2011): 162. http://dx.doi.org/10.18433/j3zc73.

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Purpose. A simple type of photoresponsive amphiphilic linear-dendritic diblock copolymer has been synthesized and investigated for its ability to act as a drug carrier. These structures contain hydrophilic polyethylene oxide monomethyl ether (PEOM) as hydrophilic block and carbosiloxane dendritic branches as hydrophobic block grafted by two and six Magneson II as azo chromophore, PEOM-Azo, 2 and PEOM-Azo, 6 respectively. Self-assembling of the amphiphilic macromolecules of PEOM-Azo, 2 and PEOM-Azo, 6, briefly were represented as PEOM-Azo [2, 6], leads to the formation of their micellar aggregates in aqueous media. Method. Their micellar properties such as critical micelle concentration (CMC), aggregation number and thereby total numbers of azo-groups in each micellar aggregates were determined. Also, they were characterized by TEM, SEM and DLS. Results. The unloaded aggregates examined under UV light (366 nm), which were observed to be smaller than 300 nm. The release patterns of the encapsulated drug molecule from these aggregates were investigated as regulated by the PEOM-Azo [2, 6] systems in trans and cis forms. Conclusion. A comparison of the release behavior of the loaded PEOM-Azo [2, 6] systems indicated that the release rate of the encapsulated active molecules from the carriers was slower when the azo moieties were in trans form as compared to that the azo in the cis form. The in vitro release behavior of drug from these polymeric systems represents potential of the carriers for controlled drug delivery. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Pashirova, Tatiana N., Andrei V. Bogdanov, Lenar I. Musin, Julia K. Voronina, Irek R. Nizameev, Marsil K. Kadirov, Vladimir F. Mironov, Lucia Ya Zakharova, Shamil K. Latypov, and Oleg G. Sinyashin. "Nanoscale isoindigo-carriers: self-assembly and tunable properties." Beilstein Journal of Nanotechnology 8 (February 1, 2017): 313–24. http://dx.doi.org/10.3762/bjnano.8.34.

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Over the last decade isoindigo derivatives have attracted much attention due to their high potential in pharmacy and in the chemistry of materials. In addition, isoindigo derivatives can be modified to form supramolecular structures with tunable morphologies for the use in drug delivery. Amphiphilic long-chain dialkylated isoindigos have the ability to form stable solid nanoparticles via a simple nanoprecipitation technique. Their self-assembly was investigated using tensiometry, dynamic light scattering, spectrophotometry, and fluorometry. The critical association concentrations and aggregate sizes were measured. The hydrophilic–lipophilic balance of alkylated isoindigo derivatives strongly influences aggregate morphology. In the case of short-chain dialkylated isoindigo derivatives, supramolecular polymers of 200 to 700 nm were formed. For long-chain dialkylated isoindigo derivatives, micellar aggregates of 100 to 200 nm were observed. Using micellar surfactant water-soluble forms of monosubstituted 1-hexadecylisoindigo as well as 1,1′-dimethylisoindigo were prepared for the first time. The formation of mixed micellar structures of different types in micellar anionic surfactant solutions (sodium dodecyl sulfate) was determined. These findings are of practical importance and are of potential interest for the design of drug delivery systems and new nanomaterials.

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Scherlund, Marie, Martin Malmsten, Peter Holmqvist, and Arne Brodin. "Thermosetting microemulsions and mixed micellar solutions as drug delivery systems for periodontal anesthesia." International Journal of Pharmaceutics 194, no. 1 (January 2000): 103–16. http://dx.doi.org/10.1016/s0378-5173(99)00366-x.

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Sumer Bolu, Burcu, Ece Manavoglu Gecici, and Rana Sanyal. "Combretastatin A-4 Conjugated Antiangiogenic Micellar Drug Delivery Systems Using Dendron–Polymer Conjugates." Molecular Pharmaceutics 13, no. 5 (April 14, 2016): 1482–90. http://dx.doi.org/10.1021/acs.molpharmaceut.5b00931.

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Iacobazzi, Rosa Maria, Ilaria Arduino, Roberta Di Fonte, Angela Assunta Lopedota, Simona Serratì, Giuseppe Racaniello, Viviana Bruno, et al. "Microfluidic-Assisted Preparation of Targeted pH-Responsive Polymeric Micelles Improves Gemcitabine Effectiveness in PDAC: In Vitro Insights." Cancers 14, no. 1 (December 21, 2021): 5. http://dx.doi.org/10.3390/cancers14010005.

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Pancreatic ductal adenocarcinoma (PDAC) represents a great challenge to the successful delivery of the anticancer drugs. The intrinsic characteristics of the PDAC microenvironment and drugs resistance make it suitable for therapeutic approaches with stimulus-responsive drug delivery systems (DDSs), such as pH, within the tumor microenvironment (TME). Moreover, the high expression of uPAR in PDAC can be exploited for a drug receptor-mediated active targeting strategy. Here, a pH-responsive and uPAR-targeted Gemcitabine (Gem) DDS, consisting of polymeric micelles (Gem@TpHResMic), was formulated by microfluidic technique to obtain a preparation characterized by a narrow size distribution, good colloidal stability, and high drug-encapsulation efficiency (EE%). The Gem@TpHResMic was able to perform a controlled Gem release in an acidic environment and to selectively target uPAR-expressing tumor cells. The Gem@TpHResMic displayed relevant cellular internalization and greater antitumor properties than free Gem in 2D and 3D models of pancreatic cancer, by generating massive damage to DNA, in terms of H2AX phosphorylation and apoptosis induction. Further investigation into the physiological model of PDAC, obtained by a co-culture of tumor spheroids and cancer-associated fibroblast (CAF), highlighted that the micellar system enhanced the antitumor potential of Gem, and was demonstrated to overcome the TME-dependent drug resistance. In vivo investigation is warranted to consider this new DDS as a new approach to overcome drug resistance in PDAC.

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Upadhyay, Ravi Kant. "Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier." BioMed Research International 2014 (2014): 1–37. http://dx.doi.org/10.1155/2014/869269.

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Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

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Paria, Shashikana, Prasenjit Maity, Rafia Siddiqui, Ranjan Patra, Shubhra Bikash Maity, and Atanu Jana. "Nanostructured Luminescent Micelles: Efficient “Functional Materials” for Sensing Nitroaromatic and Nitramine Explosives." Photochem 2, no. 1 (January 10, 2022): 32–57. http://dx.doi.org/10.3390/photochem2010004.

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Luminescent micelles are extensively studied molecular scaffolds used in applied supramolecular chemistry. These are particularly important due to their uniquely organized supramolecular structure and chemically responsive physical and optical features. Various luminescent tags can be incorporated with these amphiphilic micelles to create efficient luminescent probes that can be utilized as “chemical noses” (sensors) for toxic and hazardous materials, bioimaging, drug delivery and transport, etc. Due to their amphiphilic nature and well-defined reorganized self-assembled geometry, these nano-constructs are desirable candidates for size and shape complementary guest binding or sensing a specific analyte. A large number of articles describing micellar fluorogenic probes are reported, which are used for cation/anion sensing, amino acid and protein sensing, drug delivery, and chemo-sensing. However, this particular review article critically summarizes the sensing application of nitroaromatic (e.g., trinitrotoluene (TNT), trinitrobenzene (TNB), trinitrophenol (TNP), dinitrobenzene (DNB), etc.) and nitramine explosives (e.g., 1,3,5-trinitro-1,3,5-triazinane, trivially named as “research department explosive” (RDX), 1,3,5,7-tetranitro-1,3,5,7-tetrazocane, commonly known as “high melting explosive” (HMX) etc.). A deeper understanding on these self-assembled luminescent “functional materials” and the physicochemical behavior in the presence of explosive analytes might be helpful to design the next generation of smart nanomaterials for forensic applications. This review article will also provide a “state-of-the-art” coverage of research involving micellar–explosive adducts demonstrating the intermolecular charge/electron transfer (CT/ET) process operating within the host–guest systems.

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Ahmad, Zaheer, Afzal Shah, Muhammad Siddiq, and Heinz-Bernhard Kraatz. "Polymeric micelles as drug delivery vehicles." RSC Adv. 4, no. 33 (2014): 17028–38. http://dx.doi.org/10.1039/c3ra47370h.

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Dunuweera, Shashiprabha Punyakantha, Rajapakse Mudiyanselage Shashanka Indeevara Rajapakse, Rajapakshe Babilage Sanjitha Dilan Rajapakshe, Sudu Hakuruge Dilan Priyankara Wijekoon, Mallika Gedara Gayan Sasanka Nirodha Thilakarathna, and Rajapakse Mudiyanselage Gamini Rajapakse. "Review on Targeted Drug Delivery Carriers Used in Nanobiomedical Applications." Current Nanoscience 15, no. 4 (March 20, 2019): 382–97. http://dx.doi.org/10.2174/1573413714666181106114247.

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Targeted drug delivery (TDD) is an advanced and smart method of delivering drugs to the patients in a targeted sequence that increases the concentration of delivered drug only at the targeted body part of interest (organs/tissues/cells). This will in turn enhance efficacy of treatment by reducing side effects and the required dose of the drug. TDD ensures a certain defined minimally required constant amount of a therapeutic agent for a prolonged period of time to a targeted diseased area within the body. This helps maintain the required plasma and tissue drug levels in the body thereby avoiding any damage to the healthy tissue via the drug. Various drug carriers that are envisaged in advanced delivery systems are soluble polymers, inorganic nanoparticles, magnetic nanoparticles, biodegradable microsphere polymers (synthetic and natural), neutrophils, fibroblasts, artificial cells, lipoproteins, liposomes, micelles and immune micelle. In selecting such a vehicle, important factors to consider are chemical and physical properties drugs, side effects or cytotoxicity to healthy cells, route to be taken for the delivery of the drug, the targeted site, and the disease. As such, TDD formulations are prepared by considering the specific properties of target cells, nature of markers or transport carriers or vehicles, which convey drug to specific receptors, and ligands and physically modulated components.

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Francis, M. F., Mariana Cristea, and F. M. Winnik. "Polymeric micelles for oral drug delivery: Why and how." Pure and Applied Chemistry 76, no. 7-8 (January 1, 2004): 1321–35. http://dx.doi.org/10.1351/pac200476071321.

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The oral delivery of drugs is regarded as the optimal means for achieving therapeutic effects owing to increased patient compliance. Unfortunately, the oral delivery route is beset with problems such as gastrointestinal (GI) destruction of labile molecules, low levels of macromolecular absorption, etc. To reduce the impact of digestive enzymes and to ensure the absorption of bioactive agents in an unaltered form, molecules may be incorporated into microparticulate carriers. Many approaches to achieve the oral absorption of a wide variety of drugs are currently under investigation. Among the different polymer-based drug delivery systems, polymeric micelles represent a promising delivery vehicle especially intended for poorly water-soluble pharmaceutical active ingredients in order to improve their oral bioavailability. Recent findings of a dextran-based polymeric micelle study for solubilization of a highly lipophilic drug, cyclosporin A (CsA), will be discussed.

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Tănase, Maria Antonia, Andreia Cristina Soare, Lia Mara Diţu, Cristina Lavinia Nistor, Catalin Ionut Mihaescu, Ioana Catalina Gifu, Cristian Petcu, and Ludmila Otilia Cinteza. "Influence of the Hydrophobicity of Pluronic Micelles Encapsulating Curcumin on the Membrane Permeability and Enhancement of Photoinduced Antibacterial Activity." Pharmaceutics 14, no. 10 (October 8, 2022): 2137. http://dx.doi.org/10.3390/pharmaceutics14102137.

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Apart from its well-known activity as an antimicrobial agent, Curcumin (CURC) has recently started to arouse interest as a photosensitizer in the photodynamic therapy of bacterial infections. The aim of the present study was to evidence the influence of the encapsulation of Curcumin into polymeric micelles on the efficiency of photoinduced microbial inhibition. The influence of the hydrophobicity of the selected Pluronics (P84, P123, and F127) on the encapsulation, stability, and antimicrobial efficiency of CURC-loaded micelles was investigated. In addition, the size, morphology, and drug-loading capacity of the micellar drug delivery systems have been characterized. The influence of the presence of micellar aggregates and unassociated molecules of various Pluronics on the membrane permeability was investigated on both normal and resistant microbial strains of E. coli, S. aureus, and C. albicans. The antimicrobial efficiency on the common pathogens was assessed for CURC-loaded polymeric micelles in dark conditions and activated by blue laser light (470 nm). Significant results in the reduction of the microorganism’s growth were found in cultures of C. albicans, even at very low concentrations of surfactants and Curcumin. Unlike the membrane permeabilization effect of the monomeric solution of Pluronics, reported in the case of tumoral cells, a limited permeabilization effect was found on the studied microorganisms. Encapsulation of the Curcumin in Pluronic P84 and P123 at very low, nontoxic concentrations for photosensitizer and drug-carrier, produced CURC-loaded micelles that prove to be effective in the light-activated inhibition of resistant species of Gram-positive bacteria and fungi.

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