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Polymer micelles represent one of the most attractive drug delivery systems due to their design flexibility based on a variety of macromolecular synthetic methods. The environmentally safe chemistry in which the use or generation of hazardous materials is minimized has an increasing impact on polymer-based drug delivery nanosystems. In this work, a solvent-free green synthetic procedure was applied for the preparation of an amphiphilic diblock copolymer consisting of biodegradable hydrophobic poly(acetylene-functional carbonate) and biocompatible hydrophilic polyethylene glycol (PEG) blocks. The cyclic functional carbonate monomer 5-methyl-5-propargyloxycarbonyl-1,3-dioxane-2-one (MPC) was polymerized in bulk using methoxy PEG-5K as a macroinitiator by applying the metal-free organocatalyzed controlled ring-opening polymerization at a relatively low temperature of 60 °C. The functional amphiphilic block copolymer self-associated in aqueous media into stable micelles with an average diameter of 44 nm. The copolymer micelles were physico-chemically characterized and loaded with the plant-derived anticancer drug curcumin. Preliminary in vitro evaluations indicate that the functional copolymer micelles are non-toxic and promising candidates for further investigation as nanocarriers for biomedical applications., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Aims and Background: The fundamental objective of current study was to encapsulate Aripiprazole (ARP) within Pluronic F127 micelles to improve its aqueous solubility. The recent patents on Aripiprazole (JP2013136621) and micelles (WO2016004369A1) facilitated selection of drug and polymer., Materials and Methods: The drug-laden micelles were fabricated using thin-film hydration technique. Optimization of the micellar formulation was done by using response surface method (RSM). The Pluronic F127 concentration of 150 mg and 75 rpm rotational speed of rotary evaporator were found to be optimized conditions for formulating micelles., Results: The prepared batches were further characterized for PDI (polydispersity index), zeta potential, % DLC (% Drug loading content), % EE (% Entrapment Efficiency) and % drug release study; results of these parameters were found to be 0.228, -4.04 mV and 76.50 % and 18.56 % respectively. It was observed from the In vitro release study that 97.37 ± 1.81 % drug had released from micelles after 20h which were found about thrice as compared to that of pure drug. The optimized ARP micellar formulation was characterized using DSC (Differential Scanning Colorimetry), FT-IR (Fourier Transformed Infrared Spectroscopy), P-XRD (Powdered X-ray Diffraction Study) and TEM (Transmission Electronic Microscopy) studies. ARP-loaded micelles displayed a hydrodynamic diameter of 170.3 nm and a sphere-shaped morphology as determined by dynamic light scattering as well as TEM study., Conclusion: It is concluded that the prepared polymeric micellar system has an excellent potential to be used as a delivery carrier for Aripiprazole with increased solubility., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

To track nanocarriers, many researches adopt nanocarriers labeled with radiotracers or encapsulating near-infrared fluorescence (NIRF) dye. In this study, novel amphiphilic copolymers, methoxy poly(ethylene glycol) (mPEG)-cyanine-poly(ε-caprolactone) (PCL) (mPEG-Cy-PCL) are synthesized. mPEG-Cy-PCL are capable of performing NIRF imaging, photothermal therapy (PTT) on cancer cells and self-assembly nanocarriers. Cy-based micelles can encapsulate doxorubicin (Doxo@Cy-micelle) and achieve NIRF image-guided drug delivery. Doxo@Cy-micelles are nanosized micelles enhancing the accumulation of Doxo in tumor sites and decreasing side effects. Doxo@Cy-micelles exhibit an excellent PTT and synergistic chemotherapy of cancer via laser-triggered release of Doxo from micelles, eventually resulting in decreased cancer recurrence rates. The results show that Cy-based micelles are excellent nanocarriers for NIRF imaging and synergistic photothermal-chemotherapy of cancer., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Polymeric micelles functionalized with folate conjugated bovine serum albumin (FA-BSA) and loaded with superparamagnetic iron oxide nanoparticles (SPIONs) are investigated as a specific contrast agent for tumor targeting and magnetic resonance imaging (MRI) in vitro and in vivo. The SPIONs-loaded polymeric micelles are produced by self-assembly of amphiphilic poly(HFMA-co-MOTAC)-g-PEGMA copolymers and oleic acid modified Fe3O4 nanoparticles and functionalized with FA-BSA by electrostatic interaction. The FA-BSA modified magnetic micelles have a hydrodynamic diameter of 196.1 nm, saturation magnetization of 5.5 emu/g, and transverse relaxivity of 167.0 mM(-1) S(-1). In vitro MR imaging, Prussian blue staining, and intracellular iron determination studies demonstrate that the folate-functionalized magnetic micelles have larger cellular uptake against the folate-receptor positive hepatoma cells Bel-7402 than the unmodified magnetic micelles. In vivo MR imaging conducted on nude mice bearing the Bel-7402 xenografts after bolus intravenous administration reveals excellent tumor targeting and MR imaging capabilities, especially at 24h post-injection. These findings suggest the potential of FA-BSA modified magnetic micelles as targeting MRI probe in tumor detection., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The aqueous solution of binary mixtures of amphiphilic copolymers is a potential platform for fabricating mixed polymeric micelles for pharmaceutical applications, particularly in developing drug delivery depots for a poorly water-soluble compound. This study fabricated and investigated binary mixtures of poloxamer 403 (P403) and poloxamer 407 (P407) at varying P403:P407 molar ratios to develop a vehicle for the poorly water-soluble compound, using ibuprofen as a model drug. The cooperative formation of mixed micelles was obtained, and the solubility of ibuprofen in the binary mixtures was enhanced compared to the solubility in pure water and an aqueous single P407 solution. The binary mixture with the P403:P407 molar ratio of 0.75:0.25 at a total polymer concentration of 19% w/v exhibited the temperature dependence of micellization and sol-to-gel characteristics of the thermosensitive mixed micellar gels. It possessed suitable micellization and gelation characteristics for in situ gelling systems. The release of ibuprofen from the thermosensitive mixed micellar depots was sustained through a diffusion-controlled mechanism. The findings can aid in formulating binary mixtures of P403 and P407 to achieve the desired properties of mixed micelles and micellar gels. [ABSTRACT FROM AUTHOR]

The physicochemical properties of “smart” or stimuli-sensitive amphiphilic copolymers can be modeled as a function of their environment. In special, pH-sensitive copolymers have practical applications in the biomedical field as drug delivery systems. Interactions between the structural units of any polymer-drug system imply mutual constraints at various scale resolutions and the nonlinearity is accepted as one of the most fundamental properties. The release kinetics, as a function of pH, of a model active principle, i.e., Curcumin, from nanomicelles obtained from amphiphilic pH-sensitive poly(2-vinylpyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) tailor-made diblock copolymers was firstly studied by using the Rietger-Peppas equation. The value of the exponential coefficient, n, is around 0.5, generally suggesting a diffusion process, slightly disturbed in some cases. Moreover, the evaluation of the polymer-drug system’s nonstationary dynamics was caried out through harmonic mapping from the usual space to the hyperbolic one. The kinetic model we developed, based on fractal theory, fits very well with the experimental data obtained for the release of Curcumin from the amphiphilic copolymer micelles in which it was encapsulated. This model is a variant of the classical kinetic models based on the formal kinetics of the process.

Mixed micelles from copolymers in aqueous media have emerged as a valuable tool for producing functional polymer nanostructures with applications in nanomedicine, including drug delivery and bioimaging. In this review, we discuss the basics of mixed copolymer micelles' design, structure, and physicochemical properties. We also focus on their utilization in biomedical applications using examples from recent literature. [ABSTRACT FROM AUTHOR]

Block copolymers synthesized via Atom Transfer Radical Polymerization from alkyl acrylate and t-butyl acrylate and the subsequent hydrolysis of the t-butyl acrylate to acrylic acid were systematically varied with respect to their hydrophobic part by the variation in the alkyl chain length and the degree of polymerisation in this block. Depending on the architecture of the hydrophobic part, they had a more or less pronounced tendency to form copolymer micelles in an aqueous solution. They were employed for the preparation of IPECs by mixing the copolymer aggregates with the polycations polydiallyldimethylammonium chloride (PDADMAC) or q-chit. The IPEC structure as a function of the composition was investigated by Static Light and Small Angle Neutron Scattering. For weakly-associated block copolymers (short alkyl chain), complexation with polycation led to the formation of globular complexes, while already existing micelles (long alkyl chain) grew further in mass. In general, aggregates became larger upon the addition of further polycation, but this growth was much more pronounced for PDADMAC compared to q-chit, thereby leading to the formation of clusters of aggregates. Accordingly, the structure of such IPECs with a hydrophobic block depended largely on the type of complexing polyelectrolyte, which allowed for controlling the structural organisation via the molecular architecture of the two oppositely charged polyelectrolytes. [ABSTRACT FROM AUTHOR]

Small hydrophilic drugs are widely used for systemic administration, but they suffer from poor absorption and fast clearance. Their nanoencapsulation can improve biodistribution, targeted delivery, and pharmaceutical efficacy. Hydrophilics are effectively encapsulated in compartmented particles, such as liposomes or extracellular vesicles, which are biocompatible but poorly customizable. Polymeric vectors can form compartmental structures, also being functionalizable. Here, we report a system composed of polymeric stabilized reversed micelles for hydrophilic drugs encapsulation. We optimized the preparation procedure, and calculated the critical micellar concentration. Then, we developed a strategy for stabilization that improves micelle stability upon dilution. We tested the drug loading and delivery capabilities with creatine as a drug molecule. Prepared stabilized reversed micelles had a size of around 130 nm and a negative z-potential around −16 mV, making them functional as a drug carrier. The creatine cargo increased micelle size and depended on the loading conditions. The higher amount of loaded creatine was around 60 μg/mg of particles. Delivery tests indicated full release within three days in micelles with the lower cargo, while higher loadings can provide a sustained release for longer times. Obtained results are interesting and encouraging to test the same system with different drug cargoes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Symmetric 14-armed βCD-cored star amphiphilic block copolymers βCD-(PBO-PGL) 14 were obtained with tunable arm block lengths, high purity and low polydispersity. • Star copolymers βCD-(PBO-PGL) 14 have similar self-assembly behavior compared to linear analogues (PGL-PBO-PGL). • Polymersomes made from βCD-(PBO-PGL) 14 have different ion permeability behavior compared to linear analogues (PGL-PBO-PGL). For polymersome-based nanoreactor purposes, we herein present the synthesis and characterization of well-defined star amphiphilic copolymers composed of a beta -cyclodextrin (βCD) core and seven poly(butylene oxide)- block -polyglycidol (PBO-PGL) arms per side (βCD-(PBO-PGL) 14). The self-assembly behavior of 14-armed βCD-(PBO-PGL) 14 and PGL-PBO-PGL (linear analogues without the βCD segment) was investigated using scattering techniques for comparison. The morphologies, including vesicles and micelles, are governed by the hydrophobic-to-hydrophilic (weight) ratio, regardless of the polymer architecture (linear or star). Interestingly, despite notable differences in polymer conformation, the produced supramolecular structures were evidenced to be fairly similar on the structural point of view. We subsequently investigated the ion permeability of the membranes of the self-assemblies focusing on the impact of the presence of βCD. The results demonstrated that the βCD-containing vesicular membranes are less permeable to H+, compared with βCD-free vesicular membranes. The presence of βCD in planar membranes also influences the K+Cl− permeability to some extent. Thus, βCD-containing membranes can be considered as potential candidates in designing nano-containers towards applications where precise changes in environmental pH are required. [ABSTRACT FROM AUTHOR]

Polymeric micelles are most popular and promising drug delivery systems in recent years. Polymeric micelles are self assembled nano sized colloidal particles and size is ranges from 10-100 nm. The aim of the present study is to formulate oregano polymeric micelles to improve its aqueous solubility. Oregano loaded polymeric micelles were prepared with different polymers like PVA, PEG4000, and Pluronic F127 using solvent diffusion technique. The drug and polymer ratio were taken by Box-Behnken design. Optimization of the micellar formulation was done by using response surface method (RSM). The active constituents of oregano were analyzed by HPLC at 274 nm. The retention time of oregano in HPLC was found at 11min. The prepared polymeric micelles have low CMC value, the particle size and zeta potential was found to be in between 53.9±6.4 to 255±7.2 and -11.7±2.2 to 42.9±0.9 respectively. In vitro drug release studies revealed that 70.1 ± 1.81 % of drug released from micelles after 24h. The entrapment efficiency was found different for all formulations due to different concentration of drug and PEG used. The optimized oregano polymeric micelle formulation was further evaluated by phase contrast microscopy, FTIR analysis and in-vitro drug release kinetics. Optimized micelle formulation displayed a spherical- shaped morphology, no drugexcipient interactions and follows first order so the formulations released in sustained manner, and it also follows Higuchi and Hixson crowell release mode. It is concluded that the prepared oregano polymeric micellar system has an excellent potential delivery with increased solubility to be used orally. [ABSTRACT FROM AUTHOR]

The physicochemical properties of "smart" or stimuli-sensitive amphiphilic copolymers can be modeled as a function of their environment. In special, pH-sensitive copolymers have practical applications in the biomedical field as drug delivery systems. Interactions between the structural units of any polymer-drug system imply mutual constraints at various scale resolutions and the nonlinearity is accepted as one of the most fundamental properties. The release kinetics, as a function of pH, of a model active principle, i.e., Curcumin, from nanomicelles obtained from amphiphilic pH-sensitive poly(2-vinylpyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) tailor-made diblock copolymers was firstly studied by using the Rietger-Peppas equation. The value of the exponential coefficient, n, is around 0.5, generally suggesting a diffusion process, slightly disturbed in some cases. Moreover, the evaluation of the polymer-drug system's nonstationary dynamics was caried out through harmonic mapping from the usual space to the hyperbolic one. The kinetic model we developed, based on fractal theory, fits very well with the experimental data obtained for the release of Curcumin from the amphiphilic copolymer micelles in which it was encapsulated. This model is a variant of the classical kinetic models based on the formal kinetics of the process. [ABSTRACT FROM AUTHOR]

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In the development of subunit vaccines with purified or recombinant antigens for cancer and infectious diseases, the design of improved and safe adjuvants able to efficiently target the antigen presenting cells, such as dendritic cells, represents a crucial challenge. Nanoparticle-based antigen delivery systems have been identified as an innovative strategy to improve the efficacy of subunit vaccines. Among them, self-assembled micellar nanoparticles from amphiphilic (macro)molecules have recently emerged as promising candidates. In this short review, we report on the recent research findings highlighting the versatility and potential of such systems in vaccine delivery.

Abstract: Well‐defined copolymers synthesized by combining poly(ethylene glycol) (PEG) and amino acid based building blocks are investigated with regard to their helical rigidity and self‐assembly. Optical active block copolymers reported here are designed to have a pendant amino acid and polymerizable group, that is, isonitrile in order to induce helix formation and reduce the mobility of polymer chains by forming a hydrogen bond network so that a helix with reasonable rigidity can be obtained. Due to the amphiphilicity and a relatively shorter PEG as a coil, these polymers form micelles as observed under transmission electron microscopy in which copolymers PEG108‐b‐PPIC764 and PEG108‐b‐PPIC1020 appear to be evolving into nanoparticles with a size distribution of 100–200 nm. Circular dichroism spectroscopy is employed to study the nature of the helix and its rigidity. The folding and unfolding of polymer helix as a result of the ability of a selective solvent to form/disrupt hydrogen bonds with the peptide linkage is also discussed to highlight the responsive nature of the polymer. [ABSTRACT FROM AUTHOR]

Amphiphilic copolymers were obtained by grafting azide-terminated polyglycidol, poly(ethylene oxide), or poly(2-hydroxyethyl acrylate) chain segments onto alkyne-functionalized arborescent poly( -benzyl L-glutamate) (PBG) cores of generations G1--G3 via copper(I)-catalyzed azide--alkyne Huisgen cycloaddition (CuAAC) coupling. The alkyne functional groups on the arborescent PBG substrates were either distributed randomly or located exclusively at the end of the chains added in the last grafting cycle of the core synthesis. The location of these coupling sites influenced the ability of the arborescent copolymers to form unimolecular micelles in aqueous environments: The chain end grafting approach provided enhanced dispersibility in aqueous media and favored the formation of unimolecular micelles in comparison to random grafting. This is attributed to a better defined core-shell morphology for the copolymers with end-grafted shell segments. Aqueous solubility also depended on the type of material used for the shell chains. Coupling by CuAAC opens up possibilities for grafting a broad range of polymers on the arborescent substrates under mild conditions. [ABSTRACT FROM AUTHOR]

Nitroxide-containing amphiphilic polymers for therapeutic use were prepared in two-step procedure. Firstly, amphiphilic copolymers composed of hydrophobic poly(n -butyl acrylate) (P n BA) and hydrophilic poly[oligo(ethylene glycol) methyl ether acrylate] (POEGA) or poly(2-hydroxyethyl acrylate) (PHEA) were synthesized by simplified electrochemically mediated atom transfer radical polymerization (se ATRP). Due to the precisely-controlled structure of each polymer block proved by narrow dispersity (M w / M n < 1.19), chain-end halide functionality of macromolecules was preserved. Therefore, it was possible to efficiently convert the halide atom at the end of the chain to stable radicals via the amination of the polymer with 4-amino-2,2,6,6-tetrametylopiperydynyloksyl (4-amino-TEMPO, 4-AT). The prepared polymers are able to self-assemble in an aqueous solution into micelles with a hydrodynamic diameter of approximately 31 nm measured by dynamic light scattering (DLS) analysis. The susceptibility of the prepared micelles for biomedical applications was studied by evaluation of the effect on erythrocytes and fibroblasts and their antioxidant properties by testing of inhibition of oxidation reactions – oxidation of dihydrorhodamine 123 (DHR 123), induced by biologically relevant oxidants. The antioxidant effects of polymeric micelles were compared with those of free 4-AT. Prepared TEMPO-containing micelles exhibited biocompatibility in interaction with human erythrocytes and fibroblasts and exerted antioxidant effects. Therefore, the micelles are potentially good candidates for in vivo applications. [Display omitted] • Amphiphilic copolymers with highly preserved chain-end functionality were provided by se ATRP concept. • The precisely-controlled structure of each polymer block enables post-modification with 4-amino-TEMPO. • Polymeric micelles showed satisfactory biocompatibility and exerted antioxidant effects. • Nitroxide-containing polymer-based micelles have great potential for therapeutic use. [ABSTRACT FROM AUTHOR]

Copolymers of poly(ε-caprolactone) containing zwitterionic sulfobetaine may be used as biomedical materials. The interaction of these materials with proteins is rarely reported. In this study, amphiphilic copolymers PCL-PDEAS, PCL-PEG200-PDEAS, and PCL-PEG400-PDEAS, which contained poly{N-[2-(methacryloyloxy)ethyl]-N,N-diethyl-N-(3-sulfopropyl)-ammonium} (PDEAS), were designed and synthesized in order to explore interaction of these materials and their micelles with proteins. The structure of the copolymers was confirmed by H-NMR, Fourier transform infrared spectroscopy (FTIR), and element analysis (EA). The copolymers could form either films or micelles. The adsorption of bovine serum albumin (BSA) and fibrinogen (Fg) on the copolymer films and their micelles was studied. The results showed that BSA adsorbed on the films presented different tendencies from their micelle formulation. The protein adsorption may be related to the hydration in the shell of the micelles and the electrostatic interaction between the charges of zwitterion and the protein. The reason for the different amounts of protein adsorption between film and micelle formulation is the difference of molecular chain arrangement and charge distribution of PCLDEAS copolymer. [ABSTRACT FROM AUTHOR]

Amphiphilic block copolymers-based mixed micelles established as new drug-loading system showed superior characteristics in delivering drug such as improved solubility, enhanced stability, multifunctional carrier materials, targeting ability, and high bioavailability. Recently, there are increasing focuses on exploration and study of noninvasive routes, and the results present perfect feasibility, improved compliance and fewer aches and pains. The aim to apply mixed micelles to noninvasive alternative routes has driven massive pharmaceutical attention. Recently, various studies of micelles strategy for noninvasive routes have been conducted to overcome the inherent barriers for uptake across the gastrointestinal tract, mucosal membranes and other in vivo noninvasive barriers, and the result argues well. The objective of this article is to summary these studies and developments of mixed micelles used on noninvasive drug delivery and provide a reference for further research. [ABSTRACT FROM AUTHOR]

In this paper, a straightforward method to produce poly(3-hydroxyalkanoate)-based multicompartment micelles (MCMs) is presented. Thiol-ene addition is used to graft sequentially perfluorooctyl chains and poly(ethylene glycol) oligomers onto poly(3-hydroxyoctanoate- co-hydroxyundecenoate) oligomers backbone. Well-defined copolymers are obtained as shown by 1H NMR and size-exclusion chromatography. After nanoprecipitation in water, novel PHA-based MCMs are evidenced by cryo-transmission electron microscopy. Moreover, the cytocompatibility of MCMs is demonstrated in vitro via cell viability assay. [ABSTRACT FROM AUTHOR]

Nano-particles with controllable particle size and shape are of great interest in biomedical applications (1). From the standpoint of drug carrier design with wide applicability to a variety of hydrophobic drugs, an effective strategy would be to prepare a simple copolymer having the property to form stable polymeric micelles which can entrap hydrophobic drugs in the core (2). In this study, we have attached saturated and unsaturated long chain acid chlorides to the copolymer of PEG and dimethyl-5-aminoisophthalate via an amide linkage in order to make the copolymers amphiphilic. Further, bioactive compounds like β-carotene, which has considerable double bond unsaturation and curcumin, which has considerable aromatic unsaturation, were encapsulated in these amphiphilic copolymers which successfully demonstrated their drug loading ability. [ABSTRACT FROM AUTHOR]

Dendritic micelles formed from amphiphilic linear-dendritic hybrids based on organic linear poly (ethylene oxide) and inorganic dendritic block containing silicon atoms. The micellar structures of the synthesized copolymers were investigated by TEM images. Thus, two cluster- and flower-like structures were attributed to the first and second generations. The physical parameters of the drug-incorporated carriers, including the drug:carrier ratio, the kinetics of release and the apparent partition constant, were measured. It was observed that the loading efficiency and hydrolytic behavior of the copolymers depend on several factors, such as type of interaction between host and guest molecules, generation of the dendritic copolymers, and pH. [ABSTRACT FROM AUTHOR]

Abstract: In this study we present our efforts to homo- and co-polymerize, using group transfer polymerization (GTP), a dialkyl diester of itaconic acid, a naturally-derived unsaturated dicarboxylic acid. The monomer employed, di(n-butyl) itaconate (DBI), did not seem to polymerize by GTP to high conversion, but it displayed the remarkable ability to contribute to the polymer 1–2 units, suggesting that it would make a good end-functionalizing reagent for GTP. This was demonstrated by preparing by GTP hydrophilic homopolymers, and in situ adding to them DBI which is hydrophobic. The thus-obtained amphiphilic end-functionalized copolymers formed in water small micelles, whose aggregation numbers and radii of gyration were characterized using small-angle neutron scattering. [Copyright &y& Elsevier]

Abstract: In this paper three copolymers of polyhydroxyethylaspartamide (PHEA), bearing in the side chains polyethylene glycol (PEG) and/or hexadecylamine (C16) (PHEA-PEG, PHEA-PEG-C16 and PHEA-C16 respectively) have been studied as potential colloidal drug carriers for ocular drug delivery. The physical characterization of all three PHEA derivatives, using the Langmuir trough (LT) and micellar affinity capillary electrophoresis (MACE) techniques allowed to assume that whereas alone PHEA backbone is an inert polymer with respect to the interactions with lipid membranes and drug complexation, when PHEA chains are grafted with long alkyl chains like C16 or in combination C16 chains and hydrophilic chains like PEG, copolymers with lipid membrane interaction ability and drug complexation capability are obtained. In vitro permeability studies performed on primary cultured rabbit conjunctival and corneal epithelia cells, using PHEA-C16 and PHEA-PEG-C16 as micelle carriers for netilmicin sulphate, dexamethasone alcohol and dexamethasone phosphate, demonstrated that in all cases drug loaded PHEA-C16 and PHEA-PEG-C16 micelles provide a drug permeation across ocular epithelia greater than simple drug solutions or suspensions. In particular PHEA-PEG-C16 acts as the best permeability enhancer in our experimental model. In vivo bioavailability studies conducted with PHEA-PEG-C16 micelles loaded with dexamethasone alcohol, confirmed that this system also provides a drug bioavailability greater in comparison with that obtained with water suspension of the same drug after ocular administration to rabbits. [Copyright &y& Elsevier]

Self-assembling micelles, potentially useful as drug delivery systems for ferulic acid (FA), were obtained in aqueous media from amphiphilic α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) copolymers bearing at the polyamino acidic backbone both poly(ethyleneglycol) (2000 or 5000 Da) and hexadecylamine (C16) moieties, at a concentration of 7 × 10- 3 and 4 × 10- 3 g/l, respectively, with nanometre size and negative zeta potential. These micelles were able to entrap FA and to release it in a prolonged way in phosphate buffer solution at pH 7.4 and human plasma. These systems were also stable in storage conditions and have no cytotoxic effects on Caco-2, 16 HBE, HuDe and K562 cell lines. Moreover, PHEA-PEG2000-C16 and PHEA-PEG5000-C16 micelles were able to escape from phagocytosis by murine macrophages as a function of the surface PEGylation. [ABSTRACT FROM AUTHOR]

Abstract: Amphiphilic chitooligosaccharide-graft-poly(ε-caprolactone) (COS-g-PCL) copolymers were controllably synthesized using protection/deprotection technique of COS via trimethylsilyl groups and ring-opening polymerization of ε-caprolactone. Their crystalline properties were investigated with differential scanning calorimetry. With the increase of PCL content in graft copolymer, the values of ΔH and X c became enhanced, and T m shifted to higher temperatures. Micellar properties of amphiphilic graft copolymers were studied. Spherical micelles from COS11-g-PCL132 were prepared. However, due to the higher PCL content, the spherical micelles from COS11-g-PCL520 easily confused together so that the complicated network morphology was formed. Interestingly, hierarchical structure was observed in the formed network morphology, as being driven by the crystallization of PCL segments in micelles. Using pyrene as a model compound, the micelles from COS11-g-PCL132 copolymers can be loaded by hydrophobic therapeutic agent, potentially offering an appropriate vehicle for drug delivery. [Copyright &y& Elsevier]

Four‐arm star‐shaped poly[2‐(diethylamino)ethyl methacrylate]‐b‐poly[2‐hydroxyethyl methacrylate]s block copolymers using tetraphenylsilane (TPS) as a core with adjustable arm lengths are synthesized through two‐step atom transfer radical polymerizations. For comparison, a linear block copolymer with similar molecular weight is also prepared. The assembled star‐shaped copolymer micelles exhibit sizes of 102–139 nm and critical micelle concentrations of 1.49–3.93 mg L−1. Moreover, the bulky and rigid TPS core is advantageous for propping up the four star‐shaped arms to generate large intersegmental space. As a result, the drug‐loading capacity in the micelles is up to 33.97 wt%, much surpassing the linear counterpart (8.92 wt%) and the previously reported star‐shaped copolymers prepared using pentaerythritol as the core. Furthermore, the micelles show sensitive pH‐responsive drug release when the pH changes from 7.4 to 5.0. The in vitro cytotoxicity to Hela cells indicates that the doxorubicin (DOX)‐loaded micelles have similar anticancer activity to the pristine DOX. The combination of excellent micelle stability, high drug‐loading, sensitive pH response, and good anticancer activity endows the copolymers with promising application in drug control delivery for anticancer therapy. [ABSTRACT FROM AUTHOR]