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This manuscript serves as the starting point for in-depth research of multicomponent, statistical, methacrylate-based copolymers that potentially mimic the behavior of proteins in aqueous solutions. These synthetic macromolecules are composed of specially chosen comonomers: methacrylic acid (MAA), oligoethylene glycol methyl ether methacrylate (OEGMA475), 2-(dimethylamino)ethyl methacrylate (DMAEMA) and benzyl methacrylate (BzMA). Monomer choice was based on factors such as the chemical nature of pendant functional groups, the polyelectrolyte/polyampholyte and amphiphilic character and the overall hydrophobic–hydrophilic balance (HLB) of the obtained quaterpolymers. Their synthesis was achieved via a one-pot reversible addition fragmentation chain transfer (RAFT) polymerization in two distinct compositions and molecular architectures, linear and hyperbranched, respectively, in order to explore the effects of macromolecular topology. The resulting statistical quaterpolymers were characterized via 1H-NMR and ATR-FTIR spectroscopies. Their behavior in aqueous solutions was studied by dynamic (DLS) and electrophoretic light scattering (ELS) and fluorescence spectroscopy (FS), producing vital information concerning their self-assembly and the structure of the formed aggregates. The physicochemical studies were extended by tuning parameters such as the solution pH and ionic strength. Finally, the quaterpolymer behavior in FBS/PBS solutions was investigated to test their colloid stability and biocompatibility in an in vivo-mimicking, biological fluid environment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Henry's constant is obtained from the results of Self-Consistent field calculations to compare the surface affinity of amphiphilic copolymers of various architectures. • Spatial distribution of adsorbing segments along polymer chains has great influence on their adsorption and ultimately on colloidal stabilising properties, when used as dispersants. • For star-like polymers with identical chemical compositions, the surface affinity decreases with increasing number of arms. • For amphiphilic copolymers of the same chemical composition, dendritic polymers have the highest surface affinity. Polymer architecture is known to have significant impact on its adsorption behaviour. Most studies have been concerned with the more concentrated, "close to surface saturation" regime of the isotherm, where complications such as lateral interactions and crowding also additionally affect the adsorption. We compare a variety of amphiphilic polymer architectures by determining their Henry's adsorption constant (k H), which, as with other surface active molecules, is the proportionality constant between surface coverage and bulk polymer concentration in a sufficiently dilute regime. It is speculated that not only the number of arms or branches, but also the position of adsorbing hydrophobes influence the adsorption, and that by controlling the latter the two can counteract each other. The Self-consistent field calculation of Scheutjens and Fleer was implemented to calculate the adsorbed amount of polymer for many different polymer architectures including linear, star and dendritic. Using the adsorption isotherms at very low bulk concentrations, we determined the value of k H for these. It is found that the branched structures (star polymers and dendrimers) can be viewed as analogues of linear block polymers based on the location of their adsorbing units. Polymers containing consecutive trains of adsorbing hydrophobes in all cases showed higher level of adsorption compared to their counterparts, where the hydrophobes were more uniformly distributed on the chains. While increasing the number of branches (or arms for star polymers) also confirmed the known result that the adsorption decreased with the number of arms, this trend can be partially offset by the appropriate choice of the location of anchoring groups. [ABSTRACT FROM AUTHOR]

The copolymerization of 1,1,1,3,3,3-hexafluoroisopropylacrylate (HFIPA) and 2,2,3,3,4,4,5,5-octafluoropentyl acrylate (OFPA) with N-vinylpyrrolidone (NVP) in the presence of S,S'-dibenzyl trithiocarbonate (BTC) and polymeric RAFT agents based on fluoroacrylates were investigated. The copolymerization process proceeds in a control mode at any conditions investigated that was confirmed by the first order of reaction by monomer and SEC curves. Reactivity ratios of monomers were determined by the Fineman-Ross and Kelen-Tudos models. Aggregation behavior of copolymers at the air/water interface was studied by the Langmuir film balance technique. The influence of the composition and pH of the subphase on the surface properties of copolymers is considered. With the rise of subphase pH, as well as an increase in the mole fraction of NVP in the copolymer, the pressure of the plateau formation process increases. The morphology of LB films of various compositions was studied by atomic force microscopy. With the elevation in the proportion of NVP, a change in the size of micelles is traced. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Polymer compositions of folic acid based on an amphiphilic copolymer of N-vinylpyrrolidone with methacrylic acid, branched with triethylene glycol dimethacrylate, were developed and characterized by DLS, 1H NMR, IR spectroscopy, DSC, and TGA in solutions and in the solid state. Electron absorption spectroscopy was used to determine the effective binding constant of folic acid and the copolymer in isopropanol and in aqueous media. The behavior of nanoscale systems in water depending on the medium temperature and pH was studied, and their hydrodynamic radii were determined. Quantum chemical modeling of the structure of the intermolecular complexes was carried out, and it was shown that the hydrogen bonds formed by oxygen atoms of carboxy groups of either folic acid or methacrylic acid units and hydrogen atoms are weak. The cytotoxicity of polymer compositions with different contents of folic acid (0.5–4 wt.%) was studied on normal (FetMSC, Vero) and tumor cell cultures, namely, HeLa (human cervical adenocarcinoma, clone M-HeLa) and HepG2 (human liver carcinoma), and their high biocompatibility was demonstrated. Fluorescence microscopy was used to study the accumulation dynamics of polymer particles loaded with folic acid and a fluorescent dye, namely, zinc tetraphenylporphyrinate, in Vero and HeLa cells. Inferences were made about the prospects of the obtained compositions as targeted delivery systems. [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]

In this study, reversible addition-fragmentation chain transfer (RAFT) polymerization is utilized in order to synthesize novel hyperbranched poly(oligoethylene glycol) methyl ether methacrylate-co-tert-butyl methacrylate-co-methacrylic acid) (H-[P(OEGMA-co-tBMA-co-MAA)]) copolymers in combination with selective hydrolysis reactions. The copolymers showing amphiphilicity induced by the polar OEGMA and hydrophobic tBMA monomeric units, and polyelectrolyte character due to MAA units, combined with unique macromolecular architecture were characterized by physicochemical techniques, such as size exclusion chromatography (SEC) and 1H-NMR spectroscopy. The hyperbranched copolymers were investigated in terms of their ability to self-assemble into nanostructures when dissolved in aqueous media. Dynamic light scattering and fluorescence spectroscopy revealed multimolecular aggregates of nanoscale dimensions with low critical aggregation concentration, the size and mass of which depend on copolymer composition and solution conditions, whereas zeta potential measurements indicated pH sensitive features. In addition, aiming to evaluate their potential use as nanocarriers, the copolymers were studied in terms of their drug encapsulation and protein complexation ability utilizing curcumin and lysozyme, as a model hydrophobic drug and a model cationic protein, respectively. [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]

A series of nanoparticles (NPs) with a hydrodynamic radius from 20 to 100 nm in PBS was developed over the solubilization of hydrophobic dye methyl pheophorbide a (chlorin e6 derivative) by amphiphilic copolymers of N-vinylpyrrolidone with (di)methacrylates. Photophysical properties and biological activity of the NPs aqueous solution were studied. It was found that the dye encapsulated in the copolymers is in an aggregated state. However, its aggregation degree decreases sharply, and singlet oxygen quantum yield and the fluorescence signal increase upon the interaction of these NPs with model biological membranes—liposomes or components of a tissue homogenate. The phototoxic effect of NPs in HeLa cells exceeds by 1.5–2 times that of the reference dye chlorin e6 trisodium salt—one of the most effective photosensitizers used in clinical practice. It could be explained by the effective release of the hydrophobic photosensitizer from the NPs into biological structures. The demonstrated approach can be used not only for the encapsulation of hydrophobic photosensitizers for PDT but also for other drugs, and N-vinylpyrrolidone amphiphilic copolymers show promising potential as a modern platform for the design of targeted delivery vehicles. [ABSTRACT FROM AUTHOR]

This paper provides a review of the literature on the use of Pluronic® triblock copolymers for drug encapsulation over the last 10 years. A special focus is given to the progress of drug delivery systems (e.g. , micelles, liposomes, micro/nanoemulsions, hydrogels and nanogels, and polymersomes and niosomes); the beneficial aspects of Pluronic® triblock copolymers as biological response modifiers and as pharmaceutical additives, adjuvants, and stabilizers, are also discussed. The advantages and limitations encountered in developing site-specific targeting approaches based on Pluronic-based nanostructures in cancer treatment are highlighted, in addition to innovative examples for improving tumor cytotoxicity while reducing side effects. [Display omitted] [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]

Previous studies have demonstrated that films of sequence‐controlled amphiphilic copolymers display contact angles that depend on microblock size. This suggests that microblock length may provide a means of tuning surface and interfacial properties. In this work, the interfacial rheology of a series of sequence‐controlled copolymers, prepared through the addition of bicyclo[4.2.0]oct‐1(8)‐ene‐8‐carboxamide (monomer A) and cyclohexene (monomer B) to generate sequences up to 24 monomeric units composed of (AmBn)i microblocks, where m, n, and i range from 1 to 6. Interfacial rheometry is used to measure the mechanical properties of an air–water interface with these copolymers. As the microblock size increases, the interfacial storage modulus, G′, increases, which may be due to an increase in the size of interfacial hydrophobic domains. Small‐angle X‐ray scattering shows that the copolymers have a similar conformation in solution, suggesting that any variations in the mechanics of the interface are due to assembly at the interface, and not on solution association or bulk rheological properties. This is the first study demonstrating that microblock size can be used to control interfacial rheology of amphiphilic copolymers. Thus, the results provide a new strategy for controlling the dynamics of fluid interfaces through precision sequence‐controlled polymers. [ABSTRACT FROM AUTHOR]

Here, we report on the evaluation of critical packing parameters, PC, of l-tyrosine and ethylene glycol (PEG) amphiphilic block copolymers. The copolymers were synthesized via l-tyrosine-N-carboxyanhydride ring-opening polymerization using different amino-terminated PEGs as macroinitiators. The size and shape of their associates formed in water were investigated by transmission electron microscopy and dynamic and static light scatterings. The copolymers containing 20–30 wt. % of Tyr formed rod-like micelles. The copolymers with 30–50 wt. % of Tyr formed spherical vesicles, while those with 50–80 wt. % Tyr formed irregularly shaped polymeric nanoparticles. PC of the copolymers was estimated as the ratio of the van der Waals volume of the hydrophobic block (V) to its length (L) and the cross-sectional area of the polar block (SH). The values of SH for each copolymer were calculated according to the equation obtained from the correlation analysis of the published data. The hydrophobic block length L was calculated in three ways, i.e., assuming that polytyrosine adopts (1) stretched, (2) amyloid hairpin, or (3) Gaussian coil conformation. In the latter case, the best match of the calculated PC values with the morphology of the copolymer assemblies was observed. [ABSTRACT FROM AUTHOR]

We report the synthesis and the micellar self‐assembly in aqueous media of novel amphiphilic block copolymers. The copolymers consist of a poly[(methyl methacrylate)‐co‐(hydroxypropyl methacrylate)] statistical copolymer block and a poly[oligo(ethylene glycol) methyl ether methacrylate] block, and were synthesized by reversible addition–fragmentation chain transfer polymerization. The amphiphilic P(MMA‐co‐HPMA)‐b‐POEGMA block copolymers contain monomers of differing polarity and in varying ratios. Furthermore, HPMA segments are chosen in order to enhance hydrogen bonding interactions within the core of spherical micelles formed by the copolymers in aqueous media, as evidenced by light scattering and fluorescence spectroscopy studies. The amphiphilic copolymers are able to encapsulate the hydrophobic drugs curcumin and indomethacin as found using light scattering and spectroscopic methods. © 2021 Society of Industrial Chemistry. [ABSTRACT FROM AUTHOR]

The formation of monolayers of poly(fluoro(meth)acrylate)-b-poly(acrylic acid) (PFA-b-PAA) amphiphilic diblock copolymers at the air/water interface was characterized with the Langmuir film balance technique and atomic force microscopy. Both internal and external effects on the aggregation behaviour of the amphiphilic copolymers were considered. The structure of fluorinated hydrophobic part, as an internal factor, affects the surface behaviour of the amphiphilic copolymers through changes in the packing density of the hydrophobic core. The morphology of the LB films of all the three copolymers exhibit circular micelles with the hydrophobic core and hydrophilic coronas. The variation in pH and ionic strength leads to changes in charge distribution of PAA coronas. The surface area occupied by the PFA-b-PAA copolymers decrease with the rise of pH of subphase. The increase in salt concentration provides for the reduction of electrostatic repulsion between the hydrophilic blocks. [ABSTRACT FROM AUTHOR]

Biobased amphiphilic diblock copolymers are prepared thanks to the combination of reversible addition–fragmentation transfer (RAFT) polymerization and polymerization‐induced self‐assembly (PISA) in an eco‐friendly solvent mixture. First, the formation of a poly(acrylic acid) macroRAFT agent (PAA‐TTC) is performed in water at 70 °C. Then, in a series of experiments, the PAA‐TTC macroRAFT agent is used directly, without purification, as both chain transfer agent and stabilizing agent in the RAFT‐PISA of menthyl acrylate (MnA) in dispersion in an ethanol/water mixture. The polymerizations of MnA are fast with high final conversions and well‐controlled amphiphilic diblock copolymers are synthesized. Stable, sub‐micrometric spherical particles composed of the diblock copolymers are formed. The influence of the monomer concentration and the length of the solvophobic block on the diameter of the self‐assemblies is studied by means of dynamic light scattering and cryogenic transmission electron‐microscopy. [ABSTRACT FROM AUTHOR]

Poly(dimethylsiloxane) (PDMS) elastomer coatings containing an amphiphilic hydrolyzable diblock copolymer additive were prepared and their potential as marine antifouling and antiadhesion materials was tested. The block copolymer additive consisted of a PDMS first block and a random poly(trialkylsilyl methacrylate (TRSiMA, R = butyl, isopropyl)-co-poly(ethyleneglycol) methacrylate (PEGMA) copolymer second block. PDMS-b-TRSiMA block copolymer additives without PEGMA units were also used as additives. The amphiphilic character of the coating surface was assessed in water using the captive air bubble technique for measurements of static and dynamic contact angles. The attachment of macro- and microorganisms on the coatings was evaluated by field tests and by performing adhesion tests to the barnacle Amphibalanus amphitrite and the green alga Ulva rigida. All the additive-based PDMS coatings showed better antiadhesion properties to A. amphitrite larvae than to U. rigida spores. Field tests provided meaningful information on the antifouling and fouling release activity of coatings over an immersion period of 23 months. [ABSTRACT FROM AUTHOR]

Cannabis-based therapeutics have gained increasing attention for their potential health benefits; however, the efficient administration of hydrophobic constituents such as Δ9-tetrahydrocannabinol (THC) remains a challenge. This study explores a novel approach employing amphiphilic block copolymers to encapsulate a THC-rich extract to enhance its analgesic effect. The synthesis of amphiphilic block copolymers involves sequential ring-opening polymerization of caprolactone and a cyclic carbonate with pedant alkyne moieties. This is followed by an alkyne/azide click reaction with fatty acid derivatives. These copolymers are used to encapsulate the THC-rich extract. These extract-loaded micelles exhibit nanometric sizes, uniform distribution, and high colloidal stability in simulated gastrointestinal fluids. The release kinetic assessment of THC from the micelles displays controlled and sustained profiles, which are influenced by the hydrophobic nature of the copolymer core. In vivo evaluations using a murine model revealed the safety of micellar formulations, with minimal impact on behavior and organ health. Remarkably, micellar systems demonstrated prolonged analgesic effects in both mechanical and chemical pain models, outperforming nonencapsulated THC. This study introduces a pioneering approach to cannabis-based analgesics with prolonged activity, harnessing the potential of the tailored design of amphiphilic block copolymers to enhance the delivery and efficacy of hydrophobic cannabinoids. [Display omitted] • Block copolymers containing fatty acid derivatives were synthesized. • The in vivo analgesic activity of a cannabis derivative was enhanced. • Amphiphilic copolymers containing fatty acid are promissory vehicles for cannabinoids. [ABSTRACT FROM AUTHOR]

Well defined ABA triblock copolymer comprising a biodegradable poly(ε-caprolactone) (PCL) middle block and two pH responsive poly(acrylic acid) (PAA) outer blocks was synthesized by atom transfer radical polymerization of tert-butyl acrylate, initiated by PCL-based macroinitiator, followed by selective hydrolysis of the poly(tert-butyl acrylate) blocks. The cooperative self-assembly of the synthesized poly(acrylic acid)-block-poly(ε-caprolactone)-block-poly(acrylic acid) (PAAPCLPAA) copolymer with a temperature-responsive poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEOPPOPEO, Pluronic P85) triblock copolymer at different compositions in aqueous media was investigated. Based on experimental data, copolymer properties and composition, formation of nano-sized aggregates comprising a mixed PCL/PPO core and a mixed PEO/PAA corona is suggested. The binary mixture of PAAPCLPAA:PEOPPOPEO copolymers at molar ratio 3:1 favors the formation of mixed aggregates only, while at higher PEOPPOPEO content the aggregates coexist with pure PEOPPOPEO micelles. [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]

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]

Different types of amphiphilic macromolecular structures have been developed within recent decades to prepare the polymer particles considered as drug delivery systems. In the present research the series of amphiphilic block-copolymers containing poly(glutamatic acid) as hydrophilic, and polyphenylalanine as hydrophobic blocks was synthesized and characterized. Molecular weights for homo- and copolymers were determined by gel-permeation chromatography (GPC) and amino acid analysis, respectively. The copolymers obtained were applied for preparation of polymer particles. The specific morphology of prepared polymerosomes was proved using transmission electron microscopy (TEM). The influence on particle size of polymer concentration and pH used for self-assembly, as well as on the length of hydrophobic and hydrophilic blocks of applied copolymers, was studied by dynamic light scattering (DLS). Depending on different experimental conditions, the formation of nanoparticles with sizes from 60 to 350 nm was observed. The surface of polymersomes was modified with model protein (enzyme). No loss in biocatalytic activity was detected. Additionally, the process of encapsulation of model dyes was developed and the possibility of intracellular delivery of the dye-loaded nanoparticles was proved. Thus, the nanoparticles discussed can be considered for the creation of modern drug delivery systems. [ABSTRACT FROM AUTHOR]

The dispersion of carbon nanoparticles in water was investigated using dispersants based on block copolymers of poly(acrylic acid) (PAA) and poly(amideimide) (PAI) or a homopolymer of PAA. A diblock copolymer (PAA- block-PAI), triblock copolymer (PAA- block-PAI- block-PAA), and hetero-arm star block copolymer (PAAPAI) with similar molecular weights and PAA contents were used as dispersants. The dispersion of solutions with these polymers was investigated by ζ-potential measurements and transmission electron microscopy. The adsorption of PAI onto carbon nanoparticles was observed. The dispersion of carbon nanoparticles was measured using dynamic light scattering and UV-vis spectroscopy. The dispersibility of carbon nanoparticles increased through the series of copolymers (from most to least dispersed): PAAPAI, PAA- block-PAI, PAA- block-PAI- block-PAA, and homo-PAA. PAA-PAI copolymers behaved as effective dispersants for carbon nanoparticles in water. The presence of a hydrophobic block was essential for dispersion. The architecture of the block copolymers also influenced the dispersion of nanoparticles. Locally concentrated regions of PAA exhibited repulsive interactions, causing dispersion of nanoparticles. PAAPAI demonstrated the greatest potential as an anode binder in lithium-ion batteries because it functioned as a dispersant for the conductive additive. [ABSTRACT FROM AUTHOR]

In this study, synthesis and characterization of magnetic nanocarriers are reported for drug delivery based on the amphiphilic di-block and tri-block copolymers of poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) with surface modified super-paramagnetite Fe3O4 nanoparticles (magnetic nanoparticles (MNPs)). The synthesized block copolymers (methoxy poly(ethylene glycol) (mPEG)-PCL and PCL-PEG-PCL) were characterized by Fourier transform infrared (FT-IR), 1H nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC), and their properties such as critical micelle concentration, hydrophilicity to lipophilicity balance, and hydrolytic degradation were investigated. The block copolymers were functionalized with terminal azide groups (mPEG-PCL(N3) and (N3)PCL-PEG-PCL(N3)), and magnetic Fe3O4 nanoparticles were surface modified with poly(acrylic acid) (PAA) and propargyl alcohol (MNP-PAA-C≡CH). Magnetic nanocarriers were synthesized by click reaction between azide-terminated block copolymers and MNP-PAA-C≡CH and characterized by FT-IR, thermogravimetric analysis (TGA), dynamic light scattering (DLS), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM), and cytotoxicity was investigated by methyl thiazolyl tetrazolium assay. In vitro drug loading and release and release kinetics were investigated. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Herein, we report the synthesis and characterization of Au and Ag nanoparticles prepared by direct reaction between poly(ethylene glycol)–poly(ε-caprolactone) (PEG–PCL) block copolymers and metal precursors in DMSO at 343 K. Special attention is devoted to the structural and molecular weight effects on nanoparticle synthesis to establish general correlations between the experimental parameters and the characteristics of the obtained nanoparticles. The noble metal nanoparticles were characterized by transmission electronic microscopy (TEM), dynamic light scattering (DLS), UV–visible spectroscopy, zeta potential (ZP) and FT-IR techniques. The shape and size of the obtained nanoparticles primarily depend mainly on the chemical structure and composition (PEG–PCL) of the copolymers used in the synthesis. From density functional theory (DFT), the chemical groups responsible for metal salt reduction and stabilization of the nanoparticles have been represented using simple models. The possible solvent effects were also considered by incorporation of a polarizable continuum model (PCM) into the calculations. [ABSTRACT FROM AUTHOR]

New amphiphilic block copolymers Si-EFS x composed of a poly(dimethyl siloxane) (Si) block and a poly(4-(triethyleneglycol monomethyl ether)-2,3,5,6-tetrafluorostyrene) (EFS) block are synthesized by atom transfer radical polymerization (ATRP) starting from a bromo-terminated Si macroinitiator. Similarly, new hydrophobic block copolymers Si-FS y consisting of an Si block and a poly(pentafluorostyrene) (FS) block are prepared for comparison. X-ray photoelectron spectroscopy (XPS) analysis on block copolymer films reveals that the Si block is concentrated at the polymer-air interface, while the EFS block is located in the layers underneath. The same polymer films undergo a marked surface reconstruction after immersion in water for 7 d, as probed by XPS. This phenomenon involves the exposure of the hydrophilic oxyethylenic chains to contact water. Such surface reconstruction is even more drastic when an amphiphilic block copolymer is dispersed in a cross-linked poly(dimethyl siloxane) matrix film. [ABSTRACT FROM AUTHOR]

This work introduces a new polymeric emulsifier, polyglycerol- block-poly(ε-caprolactone), to prepare and stabilize oil-in-water nanoemulsions through the formation of a semi-solid interphase between oil and water. Nanoemulsions are prepared using representative silicone and ester oils, which are widely used for commercial consumer products. The block copolymer is homogeneously solubilized in a mixture of oil and ethanol at 70 °C, and the organic solution is dispersed in water using a conventional homogenizer. Stable nanoemulsions of 220-280 nm in mean diameter are spontaneously generated. The block copolymer is reorganized at the interface to form a robust semi-solid polymeric barrier that can prevent the entrapped oil from diffusing out to the aqueous phase. The barrier exhibits excellent stability against mechanical stresses, allowing nanoemulsions to be very stable during repeated freeze/thaw cycles. This work suggests that polyglycerol-based block copolymers can be a new promising polymeric emulsifier for stabilization of nanoemulsions of various oils. [ABSTRACT FROM AUTHOR]

ABSTRACT Four families of hyperbranched amphiphilic block copolymers of styrene (Sty, less polar monomer) and 2-vinylpyridine (2VPy, one of the two more polar monomers) or 4-vinylpyridine (4VPy, the other polar monomer) were prepared via self-condensing vinyl reversible addition-fragmentation chain transfer polymerization (SCVP-RAFT). Two families contained 4VPy as the more polar monomer, one of which possessing a Sty -b-4VPy architecture, and the other possessing the reverse block architecture. The other two families bore 2VPy as the more polar monomer and had either a 2VPy -b-Sty or a Sty -b-2VPy architecture. Characterization of the hyperbranched block copolymers in terms of their molecular weights and compositions indicated better control when the VPy monomers were polymerized first. Control over the molecular weights of the hyperbranched copolymers was also confirmed with the aminolysis of the dithioester moiety at the branching points to produce linear polymers with number-average molecular weights slightly greater than the theoretically expected ones, due to recombination of the resulting thiol-terminated linear polymers. The amphiphilicity of the hyperbranched copolymers led to their self-assembly in selective solvents, which was probed using atomic force microscopy and dynamic light scattering, which indicated the formation of large spherical micelles of uniform diameter. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 1310-1319 [ABSTRACT FROM AUTHOR]

Oil-in-water (O/W) emulsions are generally stabilized by water-soluble surfactants, which anchor to the surface of oil droplets dispersed in an aqueous solution. Our recent work introduced a new approach to stabilize nanoemulsions through the formation of a semi-solid interphase at the O/W interface using a water-insoluble amphiphilic block copolymer, methoxy poly(ethylene glycol)- block -poly(ɛ-caprolactone). However, the approach is not applicable to relatively non-polar oils due to the quick precipitation of the hydrophobic PCL block within the oil phase. Here we report on successful stabilization of non-polar liquid paraffin nanoemulsions using an amphiphilic copolymers having a new hydrophobic block comprising ɛ-caprolactone and L -lactide. The new block copolymer was reorganized at the O/W interface of liquid paraffin, generating stable nano-sized emulsions via the formation of a robust semi-solid polymeric barrier. The prepared nanoemulsions show excellent dispersion stability even under a high level of mechanical stresses during freeze/thaw cycles. [ABSTRACT FROM AUTHOR]

An effective liver-targeted delivery system was successfully developed by designing ligand-mediated nanoparticles composed of glycyrrhetinic acid (GA)-conjugated block copolymers (glycyrrhetinic acid-modified poly(ethylene glycol)-poly(β-benzyl- l-asparate, GA-PEG-PBLA) synthesized via ring-opening polymerization of the β-benzyl- l-asparate N-carboxyanhydride (BLA-NCA) monomer initiated by GA-modified polyethylene glycol (PEG). Chemical structures of the synthesized polymers were confirmed by H nuclear magnetic resonance (H NMR) and Fourier transform infrared assay (FTIR) and molecular weight determined by gel permeation chromatography (GPC). The copolymers were processed into nanoparticles for delivery of paclitaxel (PTX). In this work, the PTX-loaded nanoparticles were prepared by the emulsion-solvent evaporation method, and the physicochemical properties and cytotoxicity were investigated. The particle sizes of nanoparticles determined by dynamic light scattering measurements were around 70 nm. Transmission electron microscopy showed that the nanoparticles were spherical in shape. The results of in vitro release tests showed that the release profiles of PTX-loaded nanoparticles had a sustained drug release pattern, and PTX release from nanoparticles at pH 5.8 was much faster than that at pH 7.4. The drug release profiles were also fitted for mathematical models to analyze the release mechanism, and the Korsmeyer-Peppas model was found to be the best fit model, indicating a combined effect of diffusion and erosion mechanisms for drug release. The cytotoxicity based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against human hepatic carcinoma HepG2 cells indicated that the GA-PEG-PBLA nanoparticles had low cytotoxicity and good biocompatibility. These results indicated that the GA-PEG-PBLA nanoparticles could be a novel candidate for liver-targeted delivery of poorly water-soluble anticancer drugs. [ABSTRACT FROM AUTHOR]

In this work, TiO 2 nanoparticles were dispersed and stabilized in water using a novel type of dispersant based on tailor-made amphiphilic block copolymers of poly(ethylene glycol)-block-poly(4-vinyl pyridine) (mPEG- b -P4VP) prepared by atom transfer radical polymerization (ATRP). The performance of this new block copolymer as dispersant was compared to a polyelectrolyte dispersant commonly used for TiO 2 , sodium salt of polyacrylic acid (Na-PAA). The effect of dispersion technique and type and amount of dispersant on deagglomeration and stability of the TiO 2 aqueous suspensions were studied. After incorporation in a standard waterborne acrylic varnish formulation, dry film transparency, photocatalytic activity, and nanoparticle cluster size were also evaluated. The results show that mPEG- b -P4VP copolymer with appropriate block lengths can have a better performance than Na-PAA in terms of aqueous dispersion stabilization and cluster size reduction in the acrylic matrix. This translates into higher film transparency and photocatalytic performance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Brush copolymer analogues of PEG-PLA copolymers were produced via ATRP or ARGET ATRP. • Functionalization of either block was achieved via copolymerization. • Resulting nanoparticles have tunable stability and appropriate size/polydispersity. • High drug loading is achievable with hydrophobic drug payloads (>96% encapsulation) PL(G)A-PEG block polymers have been widely used in a variety of drug delivery applications but are inherently limited in terms of their capacity for functionalization and thus customization to specific delivery tasks. Herein, we report synthetically tunable and functionalizable brush co-polymer analogues of conventional PL(G)A-PEG polymers fabricated via atom transfer radical polymerization (ATRP) of methacrylate-based co-monomers with oligo(lactic acid) side chains in the hydrophobic block and oligo(ethylene glycol) side chains in the hydrophilic block. Block co-polymers prepared by varying the molecular weights of each block, the functionality of either block (via functional monomer copolymerization), as well as the number of lactic acid repeat units in the hydrophobic block were subsequently used to fabricate nanoparticles with sizes of 100–500 nm and tunable degradation rates via flash nanoprecipitation. The resulting nanoparticles exhibited high colloidal stability (consistent with the dense brush-like POEGMA interface), favorable in vitro cytocompatibility, and the capacity for effective drug loading (>96% encapsulation efficiency for paclitaxel and 41% even for the hydrophilic therapeutic doxorubicin hydrochloride). Furthermore, functionalization of the hydrophobic POLAMA block with methacrylic acid residues enabled controlled dissolution of the nanoparticle over time, offering potential to tune drug release via an alternative mechanism not readily accessible with conventional PLA-PEG-based block copolymers. Combining these properties with the flexible chemical compositions and the generally recognized as safe degradation properties of the brush polymer analogues, POLAMA- b- POEGMA polymers represent a highly versatile platform for nanoparticle-based drug delivery applications. [ABSTRACT FROM AUTHOR]

ABSTRACT Copper-catalyzed azide-alkyne cycloaddition (CuAAC) was used to prepare glycosylated polyethylene (PE)-poly(ethylene glycol) (PEG) amphiphilic block copolymers. The synthetic approach involves preparation of alkyne-terminated PE- b-PEG followed by CuAAC reaction with different azide functionalized sugars. The alkyne-terminated PE- b-PEG was prepared by etherification reaction between hydroxyl-terminated PE- b-PEG ( Mn ∼ 875 g mol−1) and propargyl bromide and azidoethyl glycosides were prepared by glycosylation of 2-azidoethanol. Atmospheric pressure solids analysis probe-mass spectrometry was used as a novel solid state characterization tool to determine the outcome of the CuAAC click reaction and end-capping of PE- b-PEG by the azidoethyl glycoside group. The aqueous solution self-assembly behavior of these amphiphilic glycosylated polymers was explored by TEM and dye solubilization studies. Carbohydrate-bearing spherical aggregates with the ability to solubilize a hydrophobic dye were observed. The potential of these amphiphilic glycosylated polymers to self-assemble via electro-formation into giant carbohydrate-bearing polymersomes was also investigated using confocal fluorescence microscopy. An initial bioactivity study of the carbohydrate-bearing aggregates is furthermore presented. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 5184-5193 [ABSTRACT FROM AUTHOR]

A series of carbazole-containing water-dispersible poly(acrylic acid)- b-(9-(4-vinylbenzyl)-9H-carbazole) block copolymers (poly(AA)- b-poly(VBK)) and water-soluble poly(methacrylic acid- ran-(9-(4-vinylbenzyl)-9H-carbazole)) (poly(MAA- ran-VBK)) random copolymers were synthesised in a controlled manner (i.e. low polydispersities $(\overline {M_{{\rm w}} } /\overline {M_{n} } < 1.3)$ by nitroxide-mediated polymerisation (NMP) using an SG1-based alkoxyamine initiator, BlocBuilder. Poly(AA)- b-poly(VBK) block copolymers were most easily accessed by using poly(AA) in its protected form as the macroinitiator for the 9-(4-vinylbenzyl)-9H-carbazole (VBK) block. Controlled polymerisation of MAA was accomplished using an excess of 10 mol.% SG1 relative to BlocBuilder with VBK as controlling co-monomer (initial molar feed content fVBK,0 = 0.03-0.20) in dimethylformamide at 80°C. Poly(MAA- ran-VBK) copolymers with a final VBK molar composition of FVBK < 0.30 resulted in water-soluble copolymers. In addition, as macroinitiators, poly(MAA- ran-VBK)s were sufficiently pseudo-living to reinitiate a second batch of monomer (90 mol.% methyl methacrylate with styrene) in organic solvent and by ab initio, surfactant-free emulsion polymerisation. In both cases, low polydispersity, amphiphilic block copolymers resulted $(\overline {M_{{\rm w}} } /\overline {M_{{\rm n}} } < 1.3)$. © 2012 Canadian Society for Chemical Engineering [ABSTRACT FROM AUTHOR]

Amphiphilic copolymers, synthesized from poly(ethylene glycols) and various aliphatic and aromatic diacids, which self-assemble into nanomicellar aggregates in aqueous media, were used to develop controlled release (CR) formulations of thiamethoxam (3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazinan-4-ylidene(nitro)amine) using encapsulation technique Formulations were characterised by Infrared (IR) spectroscopy, Dynamic Light Scattering (DLS) and Transmission Electron Microscope (TEM). Encapsulation efficiency, loading capacity and stability after accelerated storage test of the developed formulations were checked. The kinetics of thiamethoxam, released in sandy loam soil from the different formulations was studied. Release from the commercial formulation was faster than the CR formulations. The time taken for release of 50 % of thiamethoxam ranged from 3.56 to 6.07 days for the CR formulations. Although the diffusion exponent (n value) of thiamethoxam in soil ranged from 0.532 to 0.881 in the tested formulations showing non-Fickian transport. These CR formulations may be used in safer, effective and economic crop protection. [ABSTRACT FROM PUBLISHER]

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: Oil-in-water (O/W) emulsions are typically stabilized using water-soluble surfactants, which anchor to the surface of oil droplets dispersed in an aqueous solution. The structure of the anchored surfactants is often susceptible to physical and chemical stresses because of their highly mobile properties. Here we introduce a new approach to prepare stable silicone oil emulsions under various external stresses using a water-insoluble amphiphilic block copolymer, poly(ethylene oxide)-b-poly(ε-caprolactone) (PEO-b-PCL). Above the melting temperature (around 60°C) of the hydrophobic segment (PCL), PEO-b-PCL can be dissolved in silicone oil. When the polymer/oil mixture is dispersed in water, PEO-b-PCL is irreversibly reorganized into solid nanostructures at the interface of the aqueous/organic phases. The resulting interfacial structures provide a robust physical barrier to the emulsion coarsening processes. Accordingly, the prepared emulsions exhibit excellent structural tolerance against external stresses, including variations in pH, ionic strength, and temperature. [ABSTRACT FROM AUTHOR]

Abstract: Amphiphilic block copolymers are attracting increasing interest in the field of gene therapy, especially for transfection of striated muscles. However, little is known about the parameters affecting their transfection efficiency in vivo. These copolymers can self-assemble as micelles in certain conditions. Since micellization strongly depends on the temperature and ionic content of the preparation medium, the present paper aimed at investigating the influence of these parameters in the context of gene delivery. We first assessed the micellization of pluronic L64 and tetronic 304 at various temperatures in water, saline or Tyrode''s salts solution. Pluronic L64 can form micelles at temperatures above 37 °C in water or at 37 °C in the Tyrode''s salts solution, in the range of concentration investigated. For tetronic 304, CMC was found to be far below the concentrations used to transfer DNA. Pluronic L64 interacted with DNA only in the presence of micelles. Moreover, in vivo evaluation demonstrated that significantly improved transfection efficiency was obtained at 37 °C in Tyrode''s salts solution for pluronic L64 based formulations, compared to 4 °C and 20 °C. Such differences were not recorded with tetronic 304. Finally, optimized formulations of both tetronic 304 and pluronic L64 were able to mediate efficient transfection in dystrophic muscles. [Copyright &y& Elsevier]

Atom transfer radical polymerization (ATRP) catalyzed by N,N′,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA)/CuBr was performed to synthesize poly (tert-butyl acrylate) (PtBA-Br) with predesigned molecular weight and narrow polydispersity. Using the PtBA-Br as macroinitiator, the PtBA-block-PS copolymer was prepared through ATRP. After terminated bromine atom was converted to end-functional azide group (P(tBA-b-St)-N3), C60 end-capped PtBA-PS block copolymers (P(tBA-b-St)-C60) were synthesized by reacting C60 with P(tBA-b-St)-N3. GPC characterizations showed that C60 was chemically bonded to the end of P(tBA-b-St) chain and the products were mono-substituted. FT-IR, UV-Vis measurements confirmed that hydrolysis of P(tBA-b-St)-C60 resulted in amphiphilic C60 end-capped PAA-PS block copolymers. In additional, the photoconductivity of P(tBA-b-St)-C60 was measured. [Copyright &y& Elsevier]

Well-defined amphiphilic block copolymers polystyrene-b-poly(ethylene oxide)-b-polystyrene (PS-b-PEO-b-PS) and polystyrene-b-polyethylene oxide (PS-b-PEO) with controlled block length were synthesized using atomic-transfer radical polymerization (ATRP). The films fabricated by drop coating the block copolymer solution on mica show the marked microphase separated morphologies, which strongly depend on the block length ratio. The furrow maps of these films predict that they can be used as templates to prepare inorganic nanoparticles. [Copyright &y& Elsevier]

A series of anionic homopolymers, poly(sodium 2-(acrylamido)-2-methyl-1-propanesulfonate) (PAMPS) and amphiphilic copolymers of AMPS and sodium 11-(acrylamido)undecanoate (AaU), both block (PAMPS75-b-PAaUn), and random (P(AMPSm-co-AaUn)), were synthesized and their antiviral activity against Zika virus (ZIKV) was evaluated. Interestingly, while the homopolymers showed limited antiviral activity, the copolymers are very efficient antivirals. This observation was explained considering that under the conditions relevant to the biological experiments (pH 7.4 PBS buffer) the macromolecules of these copolymers exist as negatively charged (zeta potential about −25 mV) nanoparticles (4–12 nm) due to their self-organization. They inhibit the ZIKV replication cycle by binding to the cell surface and thereby blocking virus attachment to host cells. Considering good solubility in aqueous media, low toxicity, and high selectivity index (SI) of the PAMPS-b-PAaU copolymers, they can be considered promising agents against ZIKV infections. [ABSTRACT FROM AUTHOR]

Due to unique chelating and macrocyclic effects, crown ether compounds exhibit wide application prospects. They could be introduced into amphiphilic copolymers to provide new trigger mode for drug delivery. In this work, new amphiphilic random polymers of poly(lipoic acid-methacrylate-co-poly(ethylene glycol) methyl ether methacrylate-co-N-isopropylacrylamide-co-benzo-18-crown-6-methacrylamide (abbrev. PLENB) containing a crown ether ring and disulphide bond were synthesized via RAFT polymerization. Using the solvent evaporation method, the PLENB micelles were formed and then used to load substances, such as doxorubicin hydrochloride (DOX) and gold nanoparticles. The results showed that PLENB exhibited a variety of lowest critical solution temperature (LCST) in response to the presence of different ions, such as K+, Na+ and Mg2+. In particular, the addition of 150 mM K+ increased the LCST of PLENB from 31 to 37 °C and induced the release of DOX from the PLENB@DOX assemblies with a release rate of 99.84% within 12 h under 37 °C. However, Na+ and Mg2+ ions could not initiate the same response. Furthermore, K+ ions drove the disassembly of gold aggregates from the PLENB-SH@Au assemblies to achieve the transport of Au NPs, which is helpful to construct a K+-triggered carrier system. [ABSTRACT FROM AUTHOR]

[Display omitted] • Aggregation properties of T904 can be modulated through salt addition and changes in solution temperature. • Transition from loose cluster to compact micelles was accompanied with improved solubilization of quercetin (QN). • T904 offered superior QN solubilization in comparison to Pluronics. • QN molecules occupied the periphery of micelle core. There has been an enormous interest in improving the therapeutic efficacy of hydrophobic flavonoids through enhancement of their bioavailability. A carrier capable to effectively solubilize flavonoids is expected to support the chemical/structural integrity of flavonoid molecule, and hence, its antioxidant properties. In this paper, the effectiveness of saline solutions of an amphiphilic star block ethylene oxide-propylene oxide copolymer (Tetronic®T904) has been investigated for solubilizing quercetin (QN). T904 self-assembles in aqueous solution above its critical micellization temperature (CMT) that depends on solution concentration, temperature, pH and presence of salt. We have studied the solubilization of QN in T904 micelles at different temperature, concentration and salt (sodium chloride) concentration using scattering and spectral techniques. Our findings suggest that, at a given temperature, QN solubility is influenced by the concentration of salt and copolymer. When compared to its linear counterparts (the Pluronics®), T904 solutions offered superior solubilization. 2D NOESY NMR observations revealed that QN occupied the periphery of the hydrophobic core of micelles. Such an environment can protect the drug against oxidation in aqueous phase. [ABSTRACT FROM AUTHOR]

Chimeric or mixed nanosystems belong to the class of advanced therapeutics. Their distinctive characteristic compared with other types of nanoparticles is that they combine two or more different classes of biomaterials. These platforms have created a promising and versatile field of nanomedicine, incorporating materials that are biocompatible, such as lipids, but also functional, such as stimuli-responsive polymers. In the present work, thermoresponsive chimeric nanocarriers composed of l -α-phosphatidylcholine (Egg, Chicken) (EPC) phospholipids and poly(N-isopropylacrylamide)-b-poly(lauryl acrylate) (PNIPAM-b-PLA) block copolymers were designed and developed. Initially, model lipid bilayers with incorporated polymers and drug molecule TRAM-34 were built and studied for their thermodynamics, in order to assess the stability and functionality of the systems. Chimeric nanoparticles of EPC and PNIPAM-b-PLA were then developed and evaluated for their physicochemical properties in different medium conditions, as well as for their morphology. Polymer incorporation led to alterations in the properties and morphology of the nanoparticles, while interactions with serum proteins were absent. TRAM-34 was also incorporated inside the developed nanocarriers, followed by incorporation and release studies, which revealed the functionality of the system in elevated temperature conditions. Finally, in vitro studies on normal cells suggest the biocompatibility of these nanosystems. The proposed platforms are promising for further studies and applications in vitro and in vivo. [Display omitted] • Thermoresponsive chimeric nanocarriers with incorporated TRAM-34 were developed. • The thermotropic behavior of DPPC membranes is affected by PNIPAM-b-PLA and TRAM-34. • PNIPAM-b-PLA polymer stabilizes the membrane and leads to homogeneous nanoparticles. • EPC:PNIPAM-b-PLA nanocarriers release TRAM-34 in response to elevated temperature. • EPC:PNIPAM-b-PLA nanocarriers are biocompatible with HEK-293 cells. [ABSTRACT FROM AUTHOR]

The self-assembly of amphiphilic block-copolymers is a convenient way to obtain soft nanomaterials of different morphology and scale. In turn, the use of a biomimetic approach makes it possible to synthesize polymers with fragments similar to natural macromolecules but more resistant to biodegradation. In this study, we synthesized the novel bio-inspired amphiphilic block-copolymers consisting of poly(N-methacrylamido-d-glucose) or poly(N-vinyl succinamic acid) as a hydrophilic fragment and poly(O-cholesteryl methacrylate) as a hydrophobic fragment. Block-copolymers were synthesized by radical addition–fragmentation chain-transfer (RAFT) polymerization using dithiobenzoate or trithiocarbonate chain-transfer agent depending on the first monomer, further forming the hydrophilic block. Both homopolymers and copolymers were characterized by 1H NMR and Fourier transform infrared spectroscopy, as well as thermogravimetric analysis. The obtained copolymers had low dispersity (1.05–1.37) and molecular weights in the range of ~13,000–32,000. The amphiphilic copolymers demonstrated enhanced thermal stability in comparison with hydrophilic precursors. According to dynamic light scattering and nanoparticle tracking analysis, the obtained amphiphilic copolymers were able to self-assemble in aqueous media into nanoparticles with a hydrodynamic diameter of approximately 200 nm. An investigation of nanoparticles by transmission electron microscopy revealed their spherical shape. The obtained nanoparticles did not demonstrate cytotoxicity against human embryonic kidney (HEK293) and bronchial epithelial (BEAS-2B) cells, and they were characterized by a low uptake by macrophages in vitro. Paclitaxel loaded into the developed polymer nanoparticles retained biological activity against lung adenocarcinoma epithelial cells (A549). [ABSTRACT FROM AUTHOR]

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]