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Natural single-chain nanoparticles (SCNPs) such as proteins have inspired research into the formation and application of synthetic SCNPs. Although the latter can mimic general aspects of the self-assembly behavior of their biological counterparts, these systems remain relatively understudied. In this respect, a systematic series of amphiphilic statistical copolymers (ASC) of different molecular weights, with a hydrophilic comonomer (methacrylic acid) and varying hydrophobic comonomer to encompass methacrylates of different hydrophobicity, are synthesized. Small-angle X-ray scattering studies confirmed that SCNPs are achieved for each copolymer series when dispersed in basified water at 1% w/w. When the aggregation number of the ASC nanoparticles is close to unity the particle shape elongates resulting in a larger particle surface area to volume ratio, allowing more hydrophilic groups to locate on the particle surface tending to keep the particle surface charge density (PSC) constant. Thus, within a series, particle elongation increases with copolymer molecular weight. Structural parameters of SCNPs formed by ASCs composed of hydrophobic components with low partition coefficients are well consistent with predictions obtained from the PSC model. These results highlight the main parameters, namely molecular weight and acid content, responsible for the SCNP formation and provide insight into how specific particle morphology can be targeted., (© 2024 The Author(s). Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

A series of novel amphiphilic alternating CPEG copolymers were synthesized through an amine-epoxy click reaction comprising aliphatic amine and polyethylene glycol diglycidyl ether (PEGDE). These polymers were characterized in detail via nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA) to confirm the successful synthesis. Due to their amphiphilic structure, these polymers display thermoresponsiveness, with tunable cloud points (Tcps) that are adjustable from 20.8 °C to 46.8 °C by altering the side-chain length of the aliphatic amine, varying the mixing ratios of copolymers, the solution's pH, and salt additions. This tunable thermoresponsive behavior positions CPEG copolymers as promising candidates for a range of functional material applications.

Amphiphilic copolymers (ACs) are versatile systems with self-assembling and aggregating properties, enabling the formation of nanomaterials (NMs) such as micelles, vesicles, nanocapsules, and nanogels. These materials have been extensively explored for the delivery of various drugs and active compounds, enhancing the solubility and permeation of poorly water-soluble drugs into skin tissue. This improvement facilitates the treatment of skin diseases, including chronic conditions like cancer, as well as infections caused by bacteria, fungi, and viruses. This review summarizes recent applications of ACs in skin treatment, with a particular focus on their use in anti-cancer drug therapy. It covers the synthesis, classification, and characterization of ACs using various experimental techniques. Additionally, it discusses recent research on different drug delivery pathways using ACs, including encapsulation efficiency, release behavior, characteristics, applications, and responses to various chemical and physical stimuli (both in vivo and in vitro). Furthermore, this review provides a comprehensive analysis of the effects of ACs NMs on several skin diseases, highlighting their potential as alternative treatments.

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.

This study focused on synthesizing and characterizing PEGylated amphiphilic block copolymers with pendant linoleic acid (Lin) moieties as an alternative to enhance their potential in drug delivery applications. The synthesis involved a two-step process, starting with ring-opening polymerization of ε-caprolactone (CL) and propargylated cyclic carbonate (MCP) to obtain PEG-b-P(CL-co-MCP) copolymers, which were subsequently modified via click chemistry. Various reaction conditions were explored to improve the yield and efficiency of the click chemistry step. The use of anisole as a solvent, N-(3-azidopropyl)linoleamide as a substrate, and a reaction temperature of 60°C proved to be highly efficient, achieving nearly 100% conversion at a low catalyst concentration. The resulting copolymers exhibited controlled molecular weights and low polydispersity, confirming the successful synthesis. Furthermore, click chemistry allows for the attachment of Lin moieties to the copolymer, enhancing its hydrophobic character, as deduced from their significantly lower critical micelle concentration than that of traditional PEG-b-PCL systems, which is indicative of enhanced stability against dilution. The modified copolymers exhibited improved thermal stability, making them suitable for applications that require high processing temperatures. Dynamic light scattering and transmission electron microscopy confirmed the formation of micellar structures with sizes below 100 nm and minimal aggregate formation. Additionally, 1 H NMR spectroscopy in deuterated water revealed the presence of core-shell micelles, which provided higher kinetic stability against dilution., (© 2024 Wiley Periodicals LLC.)

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 (OEGMA 475 ), 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 1 H-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.

This manuscript presents the synthesis of hyperbranched amphiphilic poly (lauryl methacrylate-co-tert-butyl methacrylate-co-methacrylic acid), H-P(LMA-co-tBMA-co-MAA) copolymers via reversible addition fragmentation chain transfer (RAFT) copolymerization of tBMA and LMA, and their post-polymerization modification to anionic amphiphilic polyelectrolytes. The focus is on investigating whether the combination of the hydrophobic characters of LMA and tBMA segments, as well as the polyelectrolyte and hydrophilic properties of MAA segments, both distributed within a unique hyperbranched polymer chain topology, would result in intriguing, branched copolymers with the potential to be applied in nanomedicine. Therefore, we studied the self-assembly behavior of these copolymers in aqueous media, as well as their ability to form complexes with cationic proteins, namely lysozyme (LYZ) and polymyxin (PMX). Various physicochemical characterization techniques, including size exclusion chromatography (SEC) and proton nuclear magnetic resonance ( 1 H-NMR), verified the molecular characteristics of these well-defined copolymers, whereas light scattering and fluorescence spectroscopy techniques revealed promising nanoparticle (NP) self- and co-assembly properties of the copolymers in aqueous media.

Hypothesis: 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., Methodology: 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., Findings: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hydrophilic chitosan (CHT) and hydrophobic polyε-caprolactone (PCL) are well-known biocompatible and biodegradable polymers that have many applications in the biomedical and pharmaceutical fields. But the mixtures of these two compounds are considered incompatible, which makes them not very interesting. To avoid this problem and to further extend the properties of these homopolymers, the synthesis of a new graft copolymer, the fully biodegradable amphiphilic poly(ε-caprolactone-g-chitosan) (PCL-g-CHT) is described, with an unusual "reverse" structure formed by a PCL backbone with CHT grafts, unlike the "classic" CHT-g-PCL structure with a CHT main chain and PCL grafts. This copolymer is prepared via a copper-catalyzed 1,3-dipolar Huisgen cycloaddition between propargylated PCL (PCL-yne) and a new azido-chitosan (CHT-N 3 ). In order to obtain an amphiphilic copolymer regardless of the pH, chitosan oligomers, soluble at any pH, are prepared and used. The amphiphilic PCL-g-CHT copolymer spontaneously self-assembles in water into nanomicelles that may incorporate hydrophobic drugs to give novel drug delivery systems., (© 2023 Wiley-VCH GmbH.)

Membrane gas separation provides a multitude of benefits over alternative separation techniques, especially in terms of energy efficiency and environmental sustainability. While polymeric membranes have been extensively investigated for gas separations, their self-healing capabilities have often been neglected. In this work, we have developed innovative self-healing amphiphilic copolymers by strategically incorporating three functional segments: n -butyl acrylate (BA), N -(hydroxymethyl)acrylamide (NMA), and methacrylic acid (MAA). Utilizing these three functional components, we have synthesized two distinct amphiphilic copolymers, namely, AP NMA (PBA x - co -PNMA y ) and AP MAA (PBA x - co -PMAA y ). These copolymers have been meticulously designed for gas separation applications. During the creation of these amphiphilic copolymers, BA and NMA segments were selected due to their vital role in the ease of tuning mechanical and self-healing properties. The functional groups (-OH and -NH) present on the NMA segment interact with CO 2 through hydrogen bonding, thereby boosting CO 2 /N 2 separation and achieving superior selectivity. We assessed the self-healing potential of these amphiphilic copolymer membranes using two distinct strategies: conventional and vacuum-assisted self-healing. In the vacuum-assisted approach, a robust vacuum pump generates a suction force, leading to the formation of a cone-like shape in the membrane. This formation allows common fracture sites to adhere and trigger the self-healing process. As a result, AP NMA maintains its high gas permeability and CO 2 /N 2 selectivity even after the vacuum-assisted self-healing operation. The ideal CO 2 /N 2 selectivity of the AP NMA membrane aligns closely with the commercially available PEBAX-1657 membrane (17.54 vs 20.09). Notably, the gas selectivity of the AP NMA membrane can be readily restored after damage, in contrast to the PEBAX-1657 membrane, which loses its selectivity upon damage.

In this work, amphiphilic polymers synthesized from carboxylated carbon nanotubes stabilized high internal phase emulsions are demonstrated to be capable of direct extracting zearalenone and zearalanone in samples consisting of an oil-water emulsion system. Under optimal conditions, the maximum adsorption capacities for zearalenone and zearalanone are 17.27 and 13.26 mg/g. The adsorption is mainly attributed to π-π interaction, hydrophobic interaction, and hydrogen-bonding interaction for zearalenone and zearalanone. The adsorption isotherms reveal that the adsorption of zearalenone and zearalanone on amphiphilic polymers synthesized from carboxylated carbon nanotubes stabilized high internal phase emulsions follows Freundlich model with multilayer and heterogeneous adsorption due to the presence of multiple kinds of adsorption sites. The relative recoveries of the spiked zearalenone and zearalanone in corn juice samples range from 85% to 93% with relative standard deviations lower than 3.52%. The results manifest the high efficiency of amphiphilic polymers synthesized from carboxylated carbon nanotubes stabilized high internal phase emulsions for the adsorption and separation of analytes in the oil-water emulsion system. This study provides a new perspective on adsorbent engineering for the adsorption application in heterogeneous media., (© 2023 Wiley-VCH GmbH.)

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.

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.

Water-soluble forms of α-tocopherol (TP) as an effective antioxidant were obtained by encapsulating it into nanoparticles (NPs) of amphiphilic copolymers of N -vinylpyrrolidone with triethylene glycol dimethacrylate (CPL1-TP) and N -vinylpyrrolidone with hexyl methacrylate and triethylene glycol dimethacrylate (CPL2-TP) synthesized by radical copolymerization in toluene. The hydrodynamic radii of NPs loaded with TP (3.7 wt% per copolymers) were typically ca. 50 or 80 nm depending on copolymer composition, media, and temperature. Characterization of NPs was accomplished by transmission electron microscopy (TEM), IR-, and 1 H NMR spectroscopy. Quantum chemical modeling showed that TP molecules are capable to form hydrogen bonds with donor groups of the copolymer units. High antioxidant activity of both obtained forms of TP has been found by the thiobarbituric acid reactive species and chemiluminescence assays. CPL1-TP and CPL2-TP effectively inhibited the process of spontaneous lipid peroxidation as well as α-tocopherol itself. The IC 50 values of luminol chemiluminescence inhibition were determined. Antiglycation activity against vesperlysine and pentosidine-like AGEs of TP water-soluble forms was shown. The developed NPs of TP are promising as materials with antioxidant and antiglycation activity and can be used in various biomedical applications.

The development of effective anti-cancer therapeutics remains one of the current pharmaceutical challenges. The joint delivery of chemotherapeutic agents and biopharmaceuticals is a cutting-edge approach to creating therapeutic agents of enhanced efficacy. In this study, amphiphilic polypeptide delivery systems capable of loading both hydrophobic drug and small interfering RNA (siRNA) were developed. The synthesis of amphiphilic polypeptides included two steps: (i) synthesis of poly-αl-lysine by ring-opening polymerization and (ii) its post-polymerization modification with hydrophobic l-amino acid and l-arginine/l-histidine. The obtained polymers were used for the preparation of single and dual delivery systems of PTX and short double-stranded nucleic acid. The obtained double component systems were quite compact and had a hydrodynamic diameter in the range of 90-200 nm depending on the polypeptide. The release of PTX from the formulations was studied, and the release profiles were approximated using a number of mathematical dissolution models to establish the most probable release mechanism. A determination of the cytotoxicity in normal (HEK 293T) and cancer (HeLa and A549) cells revealed the higher toxicity of the polypeptide particles to cancer cells. The separate evaluation of the biological activity of PTX and anti-GFP siRNA formulations testified the inhibitory efficiency of PTX formulations based on all polypeptides (IC 50 4.5-6.2 ng/mL), while gene silencing was effective only for the Tyr-Arg-containing polypeptide (56-70% GFP knockdown).

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.

This research concerns the investigation of the preparation of polymeric nanocarriers containing a flavonoid-naringenin, xanthohumol or isoxanthohumol-based on Pluronics by the thin-film formation method. The size of the formed micelles and their stability upon dilution were evaluated using Dynamic light scattering (DLS) analysis; the high values of the drug loading and the encapsulation efficiency confirmed that the proposed systems of flavonoids delivery consisting of Pluronic P123 and F127 nanomicelles could effectively distribute the drug into tumour tissues, which makes these nanocarriers ideal candidates for passive targeting of cancer cells by the enhanced permeation and retention (EPR) effect. The in vitro cytotoxicity of proposed flavonoids in the Pluronic formulations was investigated by the SRB assay with human colon cancer cells. We designed mixed polymeric micelles, which was a successful drug delivery system for the case of naringenin not being able to enhance the bioavailability and cytotoxic activity of xanthohumol and isoxanthohumol. Furthermore, it was observed that the higher amount of polymer in the formulation achieved better cytotoxic activity.

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 1 H-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.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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 e 6 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 e 6 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.

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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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.

Nanosized systems of DOX with antitumor activity on the base of micelle-like particles of amphiphilic thermosensitive copolymers of N -vinylpyrrolidone (VP) with triethylene glycol dimethacrylate (TEGDM), and N -vinylpyrrolidone and methacrylic acid (MAA) with TEGDM were explored. They were investigated in aqueous solutions by electron absorption spectroscopy, dynamic light scattering and cyclic voltammetry. Experimental data and quantum-chemical modeling indicated the formation of a hydrogen bond between oxygen-containing groups of monomer units of the copolymers and H-atoms of OH and NH 2 groups of DOX; the energies and H-bond lengths in the considered structures were calculated. A simulation of TDDFT spectra of DOX and its complexes with the VP and TEGDM units was carried out. Electrochemical studies in PBS have demonstrated that the oxidation of encapsulated DOX appeared to be easier than that of the free one, and its reduction was somewhat more difficult. The cytotoxicity of VP-TEGDM copolymer compositions containing 1, 5 and 15 wt% DOX was studied in vitro on HeLa cells, and the values of IC 50 doses were determined at 24 and 72 h of exposure. The copolymer compositions containing 5 and 15 wt% DOX accumulated actively in cell nuclei and did not cause visual changes in cell morphology.

Low-molecular weight (MW) amphiphilic copolymers have been recently introduced as a powerful tool for the detergent-free isolation of cell membrane proteins. Herein, a screening approach is used to identify a new copolymer type for this application. Via a two-step ATRP/acidolysis procedure, a 3 × 3 matrix of well-defined poly[(butyl methacrylate)-co-(methacrylic acid)] copolymers (denoted BMAA) differing in their MW and ratio of hydrophobic (BMA) and hydrophilic (MAA) units is prepared. Subsequently, using the biologically relevant model (T-cell line Jurkat), two compositions of BMAA copolymers are identified that solubilize cell membranes to an extent comparable to the industry standard, styrene-maleic acid copolymer (SMA), while avoiding the potentially problematic phenyl groups. Surprisingly, while only the lowest-MW variant of the BMA/MAA 2:1 composition is effective, all the copolymers of the BMA/MAA 1:1 composition are found to solubilize the model membranes, including the high-MW variant (MW of 14 000). Importantly, the density gradient ultracentrifugation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blotting experiments reveal that the BMA/MAA 1:1 copolymers disintegrate the Jurkat membranes differently than SMA, as demonstrated by the different distribution patterns of two tested membrane protein markers. This makes the BMAA copolymers a useful tool for studies on membrane microdomains differing in their composition and resistance to membrane-disintegrating polymers., (© 2022 Wiley-VCH GmbH.)

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 (A m B n ) 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., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

Advances in cryogenic electron microscopy (cryo-EM) enabled routine near-atomic structure determination of membrane proteins, while nanodisc technology has provided a way to provide membrane proteins with a native or native-like lipid environment. After giving a brief history of membrane mimetics, we present example structures of membrane proteins in nanodiscs that revealed information not provided by structures obtained in detergent. We describe how the lipid environment surrounding the membrane protein can be custom designed during nanodisc assembly and how it can be modified after assembly to test functional hypotheses. Because nanodiscs most closely replicate the physiologic environment of membrane proteins and often afford novel mechanistic insights, we propose that nanodiscs ought to become the standard for structural studies on membrane proteins., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Co-delivery of chemotherapeutics in cancer treatment has been proven essential for overcoming multidrug resistance and improving the outcome of therapy. We report the synthesis of amphiphilic copolymers of N -vinyl-2-pyrrolidone and allyl glycidyl ether of various compositions and demonstrate that they can form nanoaggregates capable of simultaneous covalent immobilization of doxorubicin by the epoxy groups in the shell and hydrophobic-driven incorporation of paclitaxel into the core of nanoparticles. The structure of the obtained copolymers was characterized by 13 C NMR, IR, and MALDI spectroscopy, as well as adsorption at the water/toluene interface. A linear increase in the number-average molecular weight of amphiphilic copolymers and a decrease in the number-average diameter of macromolecular aggregates with an increase in the ratio N -vinyl-2-pyrrolidone/allyl glycidyl ether were observed. The assembled nanocarriers were characterized by DLS. The reported novel nanocarriers can be of interest for delivery and co-delivery of a wide range of pharmacological preparations and combined therapy for cancer and other deceases.

In this research, the development and investigation of novel nanoobjects based on biodegradable random polypeptides and synthetic non-degradable glycopolymer poly(2-deoxy-2-methacrylamido-d-glucose) were proposed as drug delivery systems. Two different approaches have been applied for preparation of such nanomaterials. The first one includes the synthesis of block-random copolymers consisting of polypeptide and glycopolymer and capable of self-assembly into polymer particles. The synthesis of copolymers was performed using sequential reversible addition-fragmentation chain transfer (RAFT) and ring-opening polymerization (ROP) techniques. Amphiphilic poly(2-deoxy-2-methacrylamido-d-glucose)-b-poly(l-lysine- co -l-phenylalanine) (PMAG-b-P(Lys- co -Phe)) copolymers were then used for preparation of self-assembled nanoparticles. Another approach for the formation of polypeptide-glycopolymer particles was based on the post-modification of preformed polypeptide particles with an oxidized glycopolymer. The conjugation of the polysaccharide on the surface of the particles was achieved by the interaction of the aldehyde groups of the oxidized glycopolymer with the amino groups of the polymer on particle surface, followed by the reduction of the formed Schiff base with sodium borohydride. A comparative study of polymer nanoparticles developed with its cationic analogues based on random P(Lys- co -d-Phe), as well as an anionic one-P(Lys- co -d-Phe) covered with heparin--was carried out. In vitro antitumor activity of novel paclitaxel-loaded PMAG- b -P(Lys- co -Phe)-based particles towards A549 (human lung carcinoma) and MCF-7 (human breast adenocarcinoma) cells was comparable to the commercially available Paclitaxel-LANS.

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 (PAMPS 75 -b-PAaU n ), and random (P(AMPS m -co-AaU n )), 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.

Amphiphilic copolymers consisting of alternating hydrophilic and hydrophobic units account for a major recent methodical breakthrough in the investigations of membrane proteins. Styrene-maleic acid (SMA), diisobutylene-maleic acid (DIBMA), and related copolymers have been shown to extract membrane proteins directly from lipid membranes without the need for classical detergents. Within the particular experimental setup, they form disc-shaped nanoparticles with a narrow size distribution, which serve as a suitable platform for diverse kinds of spectroscopy and other biophysical techniques that require relatively small, homogeneous, water-soluble particles of separate membrane proteins in their native lipid environment. In recent years, copolymer-encased nanolipoparticles have been proven as suitable protein carriers for various structural biology applications, including cryo-electron microscopy (cryo-EM), small-angle scattering, and conventional and single-molecule X-ray diffraction experiments. Here, we review the current understanding of how such nanolipoparticles are formed and organized at the molecular level with an emphasis on their chemical diversity and factors affecting their size and solubilization efficiency.

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 Mg 2+ . 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 Mg 2+ 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.

Polystyrene (PS) microsphere is a kind of attractive extracting medium due to its high stability in different matrices and its particle size can be controlled. The attachment of amphiphilic copolymers to the PS microsphere surface can overcome the drawback of PS relevant to its hydrophobic nature and low wettability. In our previous work, the magnetic composite based on PS microsphere (5 µm) and poly (divinylbenzene-co-N-vinylpyrrolidone, DVB-co-NVP) shell was successfully fabricated and applied for the extraction of safrole in cola drinks. However, the large size and ease of sedimentation limited its application in the enrichment of safrole from blood samples. Considering the adjustability of PS microsphere size, we synthesized the porous PS microspheres with the uniform size of 3 µm and then functionalized with Fe 3 O 4 nanoparticles and poly (DVB-co-NVP) layer in this work. Using the proposed material as extraction sorbent, a simple and fast magnetic solid phase extraction (MSPE) method coupled with HPLC was developed for quantification of safrole in the plasma. Under the optimized conditions, the response to safrole was linear in the range of 0.02-12 µg mL -1 , and the limit of detection (LOD) was 0.006 µg mL -1 . Satisfactory recoveries were obtained between 85.67% and 97.74% (spiked at 0.05, 0.2, 2 µg mL -1 ) and the relative standard deviations (RSDs) for the above spiked levels of the analyte were below 3.9% (n = 6). The adsorbent can be reused for 6 cycles without a significant loss of extraction capability., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2021. Published by Elsevier B.V.)

The utilization of enzymes for catalysis in organic solvents, while exhibiting selectivity to different substrates, is a big challenge. We report an amphiphilic random copolymer system that self-assembles with enzymes in an organic solvent to form nanoreactors. These encapsulated enzymes are not denatured and they do preserve the catalytic activity. The cross-linkable functional groups in the hydrophobic compartments of the polymers offer to control accessibility to the enzyme. This varied accessibility due to the polymer host, rather than the enzyme itself, endows the nanoreactor with an unnatural selectivity. The findings here highlight the significant potential of simple polymer-based enzyme nanoreactors to execute selective organic reactions under non-native conditions., (© 2021 Wiley-VCH GmbH.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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 1 H 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).

Matrix-assisted laser/desorption ionization (MALDI) has become a very popular ionization technique for mass spectrometry of synthetic polymers because it allows high throughput analysis of low amounts of sample while avoiding the complexity introduced by extensive multiple charging of electrospray ionization. Yet, fundamental mechanisms underlying this ionization process are not fully understood, so development of sample preparation methods remains empirical. Reliable prediction for the optimal matrix/analyte/salt system is indeed still not possible for homopolymers and it becomes even more challenging in the case of amphiphilic block copolymers where conditions dictated by one block are not compatible with MALDI requirements of the second block. In order to perform MALDI of copolymers composed of poly (ethylene oxide) (PEO) and polystyrene (PS) blocks, it was postulated here that experimental conditions suitable for both species would also be successful for PEO- b -PS. Accordingly, designs of experiments based on Quantitative Structure Activity Relationship (QSAR) analysis were first implemented, studying the influence of 19 matrices and 26 salts on the laser fluence requested for successful MALDI. This analysis first permitted to highlight correlations between the investigated 10 descriptors of matrices and salts and the analytical response, and then to construct models that permits reliable predictions of matrix/salt couples to be used for one or the other homopolymer. Selected couples were then used for MALDI of a PEO- b -PS copolymer but no general trend was observed: experimental conditions expected to work often failed whereas ionic adducts of the copolymer were clearly detected with some matrix/salt systems that were shown to badly perform for constituting homopolymers. Overall, this rules out the working assumption stating that the MALDI behavior of chains composed of PEO and PS segments should combine the behavior of the two polymeric species. Yet, although requiring a dedicated design of experiments, MALDI of the amphiphilic PEO- b -PS copolymer was achieved for the first time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pizzala, Claeys-Bruno, Monnier, Sergent and Charles.)

Objective: Bile acid sequestrants (BAS) are used extensively in the treatment of hypercholesterolaemia. This brief review aimed to describe the design and evaluation of three types of BAS: amphiphilic copolymers, cyclodextrin/poly-cyclodextrin and molecular imprinted polymers. The mechanisms underlying the action of BAS are also discussed., Key Findings: BAS could lower plasma cholesterol, improve glycemic control in patients with type 2 diabetes and regulate balance energy metabolism via receptors or receptor-independent mediated mechanisms. Different types of BAS have different levels of ability to bind to bile acids, different stability and different in-vivo activity., Conclusions: A growing amount of evidence suggests that bile acids play important roles not only in lipid metabolism but also in glucose metabolism. The higher selectivity, specificity, stability and in-vivo activity of BAS show considerable potential for lipid-lowering therapy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Vesicles, generally defined as self-assembled structures formed by single or multiple concentric bilayers that surround an aqueous core, have been widely used for biomedical applications. They can either occur naturally (e.g. exosomes) or be produced artificially and range from the micrometric scale to the nanoscale. One the most well-known vesicle is the liposome, largely employed as a drug delivery nanocarrier. Liposomes have been modified along the years to improve physicochemical and biological features, resulting in long-circulating, ligand-targeted and stimuli-responsive liposomes, among others. In this process, new nomenclatures were reported in an extensive literature. In many instances, the new names suggest the emergence of a new nanocarrier, which have caused confusion as to whether the vesicles are indeed new entities or could simply be considered modified liposomes. Herein, we discussed the extensive nomenclature of vesicles based on the suffix "some" that are employed for drug delivery and composed of various types and proportions of lipids and others amphiphilic compounds. New names have most often been selected based on changes of vesicle lipid composition, but the payload, structural complexity (e.g. multicompartment) and new/improved proprieties (e.g. elasticity) have also inspired new vesicle names. Based on this discussion, we suggested a rational classification for vesicles., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Amphiphilic antimicrobial polymers display activity against the outer bacterial cell membrane, triggering various physiological effects. We investigated the regulation of ion transport across the lipid bilayer to understand differences in biological activity for a series of amphiphilic polymethyloxazoline - polyethyleneimine copolymers. The results confirmed that the tested structures were able to increase the permeability of the lipid bilayer (LB) membrane or its rupture. Black lipid membrane (BLM) experiments show that the triggered conductance profile and its character is strongly correlated with the polymer structure and zeta potential. The polymer exhibiting the highest antimicrobial activity promotes ion transport by using a unique mechanism and step-like characteristics with well-defined discreet openings and closings. The molecule was incorporated into the membrane in a reproducible way, and the observed channel-like activity could be responsible for the antibacterial activity of this molecule., (© 2020 Wiley-VCH GmbH.)

This article presents the evaluation of diblock and triblock poly(ethylene glycol)- b -poly(1,3-trimethylene carbonate) amphiphilic copolymers (PEG-PTMCs) as excipients for the formulation of long-acting injectables (LAIs). Copolymers were successfully synthesised through bulk ring-opening polymerisation. The concomitant formation of PTMC homopolymer could not be avoided irrespective of the catalyst amount, but the by-product could easily be removed by gel chromatography. Pure PEG-PTMCs undergo faster erosion in vivo than their corresponding homopolymer. Furthermore, these copolymers show outstanding stability compared to their polyester analogues when formulated with amine-containing reactive drugs, which makes them particularly suitable as LAIs for the sustained release of drugs susceptible to acylation.

In this work, surface-modifying amphiphilic additives (SMAAs) were synthesized via hydrosilylation using various polymethylhydrosiloxanes (PMHS) and allyl-terminated polyethylene glycol monomethyl ethers (APEG) of varying molecular weights. The additives synthesized were incorporated into a hydrophobic, self-stratifying siloxane-polyurethane (SiPU) coating system to produce an amphiphilic surface. Contact angle experiments and atomic force microscopy (AFM), in a dry and hydrated state, were performed to assess changes in surface wettability and morphology. The antifouling and fouling-release (AF/FR) performances were evaluated by performing laboratory biological assays using the marine bacterium Cellulophaga lytica , the microalga Navicula incerta , the macroalga Ulva linza , the barnacle Amphibalanus amphitrite , and the marine mussel, Geukensia demissa . Several of the formulations showed improved AF/FR performance vs the base SiPU and performed better than some of the commercial standard marine coatings. Formulations containing SMAAs with a low grafting density of relatively high molecular weight PEG chains showed the best performance overall.

Hydrated copolymers of N -vinylpyrrolidone (VP) with triethylene glycol dimethacrylate as a promising platform for biologically active compounds (BAC) were investigated by different physical chemical methods (dynamic light scattering, infrared spectroscopy, thermal gravimetric analysis, and differential scanning calorimetry) and the quantum chemical modeling of water coordination by the copolymers in a solution. According to the quantum chemical simulation, one to two water molecules can coordinate on one O-atom of the lactam ring of VP units in the copolymer. Besides the usual terminal coordination, the water molecule can form bridges to bind two adjacent C=O groups of the lactam rings of VP units. In addition to the first hydration shell, the formation of a second one is also possible due to the chain addition of water molecules, and its structure depends on a mutual orientation of C=O groups. We showed that N , N -dimethylbiguanidine hydrochloride (metformin) as a frontline drug for the treatment of type 2 diabetes mellitus can be associated in aqueous solutions with free and hydrated C=O groups of the lactam rings of VP units in studied copolymers. Based on the characteristics of the H-bonds, we believe that the level of the copolymer hydration does not affect the behavior and biological activity of this drug, but the binding of metformin with the amphiphilic copolymer will delight in the penetration of a hydrophilic drug across a cell membrane to increase its bioavailability.

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., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

It is reported that low concentration of amphiphilic triblock copolymers of pMeOx-b-pTHF-b-pMeOx structure (TBCPs) improves gene expression in skeletal muscle upon intramuscular co-injection with plasmid DNA. Physicochemical studies carried out to understand the involved mechanism show that a phase transition of TBCPs under their unimer state is induced when the temperature is elevated from 25 to 37 °C, the body temperature. Several lines of evidences suggest that TBCP insertion in a lipid bilayer causes enough lipid bilayer destabilization and even pore formation, a phenomenon heightened during the phase transition of TBCPs. Interestingly, this property allows DNA translocation across the lipid bilayer model. Overall, the results indicate that TBCPs exhibiting a phase transition at the body temperature is promising to favor in vivo pDNA translocation in skeletal muscle cells for gene therapy applications., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hypothesis: Liquid-liquid phase separation (LLPS) can provide micron-sized liquid compartments dispersed in an aqueous medium. This phenomenon is increasingly appreciated in natural systems, e.g., in the formation of intracellular membraneless organelles, as well as in synthetic counterparts, such as complex coacervates and vesicles. However, the stability of these synthetic phase-separated microstructures versus coalescence is generally challenged by the presence of salts and/or surfactants, which narrows the range of possible applications. We propose a new strategy to obtain micron-sized liquid domains via LLPS, by mixing an amphiphilic copolymer with surfactants and sodium citrate in water at room temperature., Experiments: Combining Confocal Laser Scanning Microscopy (CLSM) and Differential Scanning Calorimetry (DSC) with Dissipative Particle Dynamics (DPD) simulations, we map the phase diagram to detect LLPS and address the presence and morphology of these microscopic domains. This mapping in turn provides a first mechanistic hypothesis for the formation of such confined polymer-rich microenvironments., Findings: LLPS is driven by the phase behavior of the copolymer in water and by its associative interactions with surfactants, combined with the water-sequestering ability of salting-out electrolytes. The key factor for LLPS and formation of microdomains is the entropy-driven dehydration of the copolymer head groups, which can be quantified through the Free Water Content (FWC). Interestingly, the internal morphology of the LLPS microdomains is finely controlled by the ratio between nonionic and anionic surfactants. Beside its applicative potential, this approach represents a tool for designing synthetic mimics that improve our understanding of the occurrence of LLPS in cells., (Copyright © 2019. Published by Elsevier Inc.)

The new polymeric systems for delivery in cosmetology applications were prepared using self-assembling amphiphilic graft copolymers. The synthesis based on "click" chemistry reaction included grafting of azide-functionalized polyethylene glycol (PEG-N 3 ) onto multifunctional polymethacrylates containing alkyne units. The latter ones were obtained via atom transfer radical polymerization (ATRP) of alkyne-functionalized monomers, e.g., ester of hexynoic acid and 2-hydroxyethyl methacrylate (AlHEMA) with methyl methacrylate (MMA), using bromoester-modified retinol (RETBr) as the initiator. Varying the content of alkyne moieties adjusted by initial monomer ratios of AlHEMA/MMA was advantageous for the achievement of a well-defined grafting degree. The designed amphiphilic graft copolymers P((HEMA- graft -PEG)- co -MMA), showing tendency to micellization in aqueous solution at room temperature, were encapsulated with arbutin (ARB) or vitamin C (VitC) with high efficiencies (>50%). In vitro experiments carried out in the phosphate-buffered saline solution (PBS) at pH 7.4 indicated the maximum release of ARB after at least 20 min and VitC within 10 min. The fast release of the selected antioxidants and skin-lightening agents by these micellar systems is satisfactory for applications in cosmetology, where they can be used as the components of masks, creams, and wraps.

Poly[poly(ethylene glycol) methacrylate]s with OH groups on the PEG side chains [poly(PEGOHMA)s] were synthesized using ruthenium-catalyzed living radical polymerization (Ru-LRP) to diversify the polymer design of PEGylated methacrylate-based copolymers. Poly(PEGOHMA)s could not be prepared using the approach previously reported for the synthesis of poly[poly(ethylene glycol) methyl ether methacrylate [poly(PEGMA)]; therefore, the polymerization was adapted for poly(PEGOHMA)s. As a result, both homopolymerization and random and block copolymerization of PEGOHMA with other hydrophobic monomers were successfully achieved, resulting in the preparation of amphiphilic random block and star polymers. The solution and bulk properties of PEGOHMA-based (co)polymers were markedly different from those of PEGMA-based (co)polymers. By reacting the OH groups with biotin, protein-poly(PEGOHMA) conjugates were successfully prepared; however, it was not possible to prepare protein-polymer conjugates using terminal biotinylated PEGMA-based copolymers, owing to the steric hindrance of the unreactive PEG side chains.

Polymersomes, also called polymeric vesicles, are self-assembled by amphiphilic copolymers. Due to their unique characters, polymersomes are attracting more and more interest as an important class of vehicles for nanopharmaceuticals. In this chapter, various methods to prepare and characterize polymersomes are introduced systematically with several applicable examples. In addition, the advantages and disadvantages of each method were compared and analyzed with the aim to help readers choose the appropriate method in the process of experiments. Although some methods we introduced here are effective in preparing and characterizing polymersomes, the remaining challenge in this filed is to develop new tools. The reason is that polymersome is a kind of complex nanostructure, and some minor factors can affect the formation of polymersome. Meanwhile, more advanced technology should be developed to precisely determine the structure of some complex polymersomes such as multilayer polymersomes.

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.)