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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).

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.)

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.)

We report the computational analysis, synthesis and characterization of folate functionalized poly(styrene-alt-maleic anhydride), PSMA for drug delivery purpose. The selection of the proper linker between the polymer and the folic acid group was performed before conducting the synthesis using Density Functional Theory (DFT). The computational results showed the bio-degradable linker 2, 4-diaminobutyric acid, DABA as a good candidate allowing flexibility of the folic acid group while maintaining the pH sensitivity of PSMA, used as a trigger for drug release. The synthesis was subsequently carried out in multi-step experimental procedures. The functionalized polymer was characterized using InfraRed spectroscopy, Nuclear Magnetic Resonance and Dynamic Light Scattering confirming both the chemical structure and the pH responsiveness of PSMA-DABA-Folate polymers. This study provides an excellent example of how computational chemistry can be used in selection process for the functional materials and product characterization. The pH sensitive polymers are expected to be used in delivering anti-cancer drugs to solid tumors with overly expressed folic acid receptors., (Crown Copyright © 2016. Published by Elsevier B.V. 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‐N3). 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. [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]

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

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 (IC50 4.5–6.2 ng/mL), while gene silencing was effective only for the Tyr-Arg-containing polypeptide (56–70% GFP knockdown). [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel gradient-like copolymers were synthesized by RAFT polymerization. • Copolymerization of N -vinylsuccinimide with O-cholesteryl (meth)acrylate was studied. • Amphiphilic poly(vinylsuccinamic acid-co-cholesteryl (meth)acrylate)s were obtained. • Stable nanoparticles of 100–400 nm were produced by several techniques. • Irinotecan delivery systems with high loading and inhibitory activity were developed. Today, biocompatible and bioinspired well-defined copolymers with the ability to form nanoparticles are of great interest as potential drug delivery systems. In this study, we report the synthesis of novel biocompatible copolymers from monomers with different activity and capable of forming gradient copolymers by RAFT polymerization. In particular, the copolymerization of N -vinylsuccinimide (VSI) and O -cholesteryl (meth)acrylate (Ch(M)A) mediated by S,S' -dibenzyl trithiocarbonate (DBTTC) has been thoroughly studied by varying the monomer ratio and the ratio of monomer to RAFT agent. Important dependencies such as molecular weight and monomer conversion versus time, and molar fraction of monomer units as a function of monomer conversion were investigated. The obtained copolymers were thoroughly characterized using a number of physicochemical methods such as 1H NMR, 1H–13C HSQC and ATR-IR-spectroscopy, size-exclusion chromatography, static and dynamic light-scattering, as well as thermogravimetric analysis. In addition, the reactivity ratios of VSI and ChMA were determined and the dyad and triad compositions of the copolymers were calculated from the obtained values. The synthesized P(VSI- co -Ch(M)A) were subjected to selective hydrolysis of succinimide ring to convert it into succinamic acid. This approach yields a set of bioinspired amphiphilic copolymers based on N -vinylsuccinamic acid (VSAA) and Ch(M)A. The synthesized series of P(VSI- co- Ch(M)A) and P(VSAA- co -Ch(M)A) were used to obtain nanoparticles by nanoprecipitation or self-assembly via direct dissolution in aqueous medium. In addition, the method of surface hydrolysis of VSI units in pre-formed P(VSI- co- Ch(M)A) nanoparticles was applied to produce nanoparticles with hydrophilic negatively charged surface and enhanced stability. All techniques were optimized to prepare nanoparticles with characteristics suitable for systems considered for drug delivery. Successful loading of the antitumor drug irinotecan into nanoparticles was achieved with high encapsulation efficacies. The storage stability of empty and irinotecan loaded nanoparticles were studied in various media (water, saline solution, serum containing cell culture medium) under room and refrigerator conditions. The developed empty nanoparticles exhibited low rate of uptake by macrophages and low cytotoxicity to irinotecan-sensitive colon cancer cells (Caco-2). In turn, the irinotecan-loaded nanoparticles demonstrated inhibitory activity against Caco-2 cells comparable to the free drug. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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

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]

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. [ABSTRACT FROM AUTHOR]

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.

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Small-molecule drugs often have limited solubility, display rapid clearance or poor selectivity that leads to undesired side-effects. Although prodrug strategies can improve solubility and lower toxicity, activation 'on demand' as well as targeted transport of prodrugs remains a challenge in drug delivery. Responsive polymeric nanoparticles can help meet these challenges with the encapsulation or conjugation of drugs, allowing release at the target site upon triggering by an internal or external stimulus. The adaptable design of polymeric nanoparticles allows them to play a vital role in achieving a specific and desired response following application of a specific stimulus. Here, the most recent progress in responsive polymeric nanoparticles is reviewed with a focus on the chemical properties of the utilized polymers. © 2017 Society of Chemical Industry [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]

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]

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

Amphiphilic triblock copolymers, based on hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly( l,l-lactide) (PLLA) blocks, were used as the matrix material for the preparation of tetracycline-loaded microspheres. The morphology and thermal properties of the biodegradable microspheres were evaluated. SEM showed the predominance of the spherical shape, however, it was possible to distinguish three patterns: rough or smooth surface or uneven collapsed volume. The FTIR analysis indicated good mechanical stability and structural integrity of the PLLA-PEG-PLLA copolymer's microspheres enclosing tetracycline. By thermal analysis it was possible to see the marginal influence of tetracycline on the glass transition and melting temperatures of the PLLA-PEG-PLLA triblock copolymer, while the results by TG indicated the presence of tetracycline in the inner structure of the microspheres, which thermal decomposition leading to char formation was triggered by the drug's presence. [ABSTRACT FROM AUTHOR]

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

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

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]