Search Results (256)

The controlled synthesis of long hydrophobic blocks in amphiphilic block copolymers remains challenging in living anionic ring-opening polymerization (LAROP), particularly when competing effects such as back-biting and solubility limitations are involved. In this study, we investigated the temperature-dependent growth of poly(allyl glycidyl ether) (PAGE) blocks in PEO-b-PAGE block copolymers synthesized via LAROP using potassium naphthalenide as a co-initiator. Systematic variation in reaction parameters revealed that reaction temperature plays a significant role in governing effective PAGE block extension and dispersity control. Lower temperatures facilitated the formation of longer PAGE blocks with dispersities below 1.1 and DP values approaching targeted compositions, whereas elevated temperatures limited block growth. A group method of data handling (GMDH) polynomial neural network was employed as an auxiliary tool to prioritize influential variables within the experimental design matrix. The GMDH-guided analysis consistently identified temperature as the most influential variable, in agreement with experimental observations. These results provide quantitative insight into the temperature-controlled propagation behavior of PAGE in LAROP systems and offer a practical framework for improving block copolymer synthesis under kinetically and thermodynamically constrained conditions. Full article

The comparison of the ability of poly(phenylene sulfone) (PPSU), a recently introduced alternative membrane polymer, with established poly(ether sulfone) (PESU), both in combination with tailored amphiphilic block copolymer additives to improve ultrafiltration (UF) membrane separation and anti-fouling performance is the focus of this work. Different poly(alkylene oxide)-containing tri- and multiblock polymers with hydrophobic blocks analogous to the respective base polymer, PPSU or PESU, of varied length were used as additives in the casting solution. Membranes were subsequently prepared via film casting and a liquid non-solvent-induced phase separation (NIPS) process. The rheological properties and thermodynamic stability of the casting solutions were investigated. At the same mass concentration, PPSU-based casting solutions show overall higher viscosity that is also more sensitive to the presence of additives compared with PESU-based solutions. PPSU-based casting solutions also have lower tolerance to non-solvents. By adding certain block copolymers in ratios of up 10 wt.% relative to the base polymer, it is possible to increase the UF performance of the membranes of PPSU and PESU. An increase in the block length of the hydrophobic block of PESU leads to a reduction in pure water permeance (PWP), whereas for PPSU, PWP is increased by the addition of additives. Especially additives with shorter PESU or PPSU block length, i.e., with a larger fraction of poly(ethylene oxide) blocks in the casting solution, seem to act as additional pore-forming agents. The water contact angle can be decreased for both additive systems, indicating a more hydrophilic membrane surface. Finally, using flower soil extract as a model substance for surface water, interesting candidates of additives that enable fouling reduction with competitive UF performance were identified for PESU and PPSU membranes. Full article

The long-term structural stability of ordered mesoporous silica (OMS) materials—specifically the durability of their pore architecture and pore lattice over time—is critical for their performance in catalysis, separation, drug carrier and nanoconfinement applications. SBA-15-type silica materials are synthesized via two different routes, namely the conventional “liquid crystal templating” (LCT) and the much less common “true liquid crystal templating” (TLCT) of micellar structures formed by the amphiphilic block copolymer Pluronic P123 in water. Here, we report that SBA-15 materials age very differently depending on the synthesis route: Under ambient conditions, OMS materials obtained via the LCT route undergo significant structural changes over time, especially in microporous regions, while SBA-15 materials obtained via the TLCT route show less or even no structural changes even after a year of storage. We attribute this enhanced aging stability of TLCT materials to their narrow mesopore size distribution and their much lower degree of microporosity. Full article

Small-molecule immunomodulators have become important components of modern immunotherapy by targeting immune checkpoints, cytokine signaling pathways, metabolic enzymes, and intracellular kinases. Despite pharmacological rationale, many of these agents underperform clinically due to unfavorable physicochemical properties, rapid systemic clearance, limited target accumulation, and dose-limiting toxicities, reflecting inadequate exposure control rather than a lack of target validity. Polymeric micelles, formed through the self-assembly of amphiphilic block copolymers, offer a versatile delivery platform to address these challenges by enhancing solubility, modulating pharmacokinetics, enabling stimuli-responsive release, and facilitating targeted or synchronized co-delivery. In this review, we classify representative small-molecule immunomodulators according to their immunological targets and examine the delivery constraints that shape their therapeutic performance. We then discuss design principles of polymeric micelle systems, including solubilization-driven formulations, microenvironment-responsive architectures, spatial targeting strategies, and co-delivery approaches that align cytotoxic and immunomodulatory mechanisms. Attention is given to the distinction between direct immunomodulators and cytotoxic agents that induce immunogenic cell death, highlighting how micelle-based delivery can enhance efficacy through improved exposure control. By integrating immunopharmacology with formulation science, this review outlines how polymeric micelles may advance the efficacy and safety of small-molecule immunomodulators and identifies key considerations for future translational development. Full article

Amphiphilic copolymers based on polystyrene and polyglycidol combine the chemical inertness of polystyrene with the biocompatibility of polyglycidol, making them attractive materials for polymeric micelles. While comb-like architectures have been explored to control micellization behavior and biological response, a direct comparison between comb-like and coil-comb topologies in polystyrene–polyglycidol copolymers at identical polyglycidol content remains insufficiently investigated. In this work, amphiphilic comb-like and coil-comb polystyrene–polyglycidol copolymers were synthesized via copper-catalyzed azide–alkyne click chemistry by grafting a monoalkyne-terminated polyglycidol precursor onto azide-functionalized random and block styrene copolymers. The copolymers were characterized by size exclusion chromatography and nuclear magnetic resonance. Polymeric micelles were prepared by nanoprecipitation, and their self-assembly in aqueous solution was investigated by critical micelle concentration determination, dynamic and electrophoretic light scattering, and atomic force microscopy. Both copolymers formed stable aqueous dispersions and exhibited comparable critical micelle concentrations. At identical polyglycidol content, the random copolymer formed a uniform, monomodal micellar population, whereas the block-based coil-comb architecture led to bimodal size distributions, indicating the coexistence of two distinct micellar populations. The investigated systems showed low cytotoxicity and did not induce significant oxidative stress within the studied concentration range. On isolated rat brain sub-cellular fractions (synaptosomes, mitochondria and microsomes), administered alone, the comb-like and coil-comb polystyrene-polyglycidol copolymers did not reveal statistically significant neurotoxic effects. The results demonstrate that macromolecular architecture plays a key role in governing micellar organization and in vitro biological response in polystyrene–polyglycidol copolymers, highlighting their potential as architecture-controlled polymer-based nanocarriers. Full article

Background: Pentamidine isethionate (PTM) and miltefosine (MF) are clinically relevant antiparasitic agents whose use is limited by toxicity, emerging resistance, and the lack of effective co-delivery strategies. Tetronic^® 1307 (T1307), an amphiphilic and thermoresponsive block copolymer, was investigated as a carrier to enable their combination therapy. Methods: PTM and MF were formulated in T1307-based micelles and thermoresponsive gels. The systems were characterized by small-angle neutron scattering (SANS), dynamic light scattering (DLS), and nuclear magnetic resonance spectroscopy (NMR). Antiparasitic activity was evaluated against Leishmania major promastigotes. Results: MF formed stable micelles that efficiently incorporated PTM, generating a “drug-in-drug” architecture. While T1307 alone showed limited PTM loading, MF promoted mixed micelle formation and enhanced PTM incorporation. At physiological temperature and adequate copolymer concentrations, drug-loaded micelles formed thermoreversible gels suitable for topical application. The combined formulations preserved drug activity and exhibited synergistic effects against L. major. Conclusions: T1307 is a promising platform for the co-delivery of PTM and MF, enabling synergistic combination therapy and thermoresponsive gel formation with potential to reduce systemic toxicity and improve treatment administration. Full article

Τhe self-assembly behavior of a series of amphiphilic diblock copolymers, each consisting of a hydrophilic poly(N-vinyl pyrrolidone) (PNVP) block and a hydrophobic block derived from n-alkyl vinyl esters, namely poly(vinyl butyrate) (PVBu), poly(vinyl decanoate) (PVDc), and poly(vinyl stearate) (PVSt), in aqueous solutions was investigated. Dynamic and static light scattering (DLS and SLS) techniques were employed to monitor the micellization behavior. In addition, the self-assembled structures were observed with Transmission Electron Microscopy (TEM). The effect of the nature of the hydrophobic block, the copolymer composition and the copolymer molecular weight on the self-assembly properties was thoroughly examined. The encapsulation of curcumin and indomethacin within the dry cores of the micellar structures was conducted in aqueous solutions for all block copolymers at various curcumin/indomethacin-to-polymer mass ratios. UV-Vis spectroscopy was used to evaluate the drug-loading capacity and efficiency (%DLC and %DLE). In several cases, the encapsulation of both hydrophobic drugs was found to be nearly quantitative. Combined with the observed stability of the micellar structures, these findings suggest that the block copolymers demonstrate significant potential as carriers for drug delivery applications. Full article

The association behavior of amphiphilic block copolymers of N-vinyl pyrrolidone (NVP) and several vinyl esters (Ves) (PNVP-b-PVEs), as exemplified by vinyl butyrate (VBu), vinyl decanoate (VDc), and vinyl stearate (VSt), was studied in tetrahydrofuran (THF), which serves as the selective solvent for the PVE blocks. Static (SLS) and dynamic light scattering (DLS) techniques were adopted as the tools to investigate micellar properties and acquire information regarding the degree of association, the hydrodynamic radii, and the shape of the aggregates. In addition, CONTIN analysis provided insights concerning the association equilibria in THF solutions. The effect of the chemical structure of the corona-forming PVE block on the association process was investigated. Finally, the experimental results were compared with those obtained in previous studies describing the micellization properties of block copolymers consisting of PNVP and polymethacrylate blocks in the same selective solvent. Full article

Background: Glucocorticoids are an important class of therapeutics used in a variety of applications, including allotransplantations. Dexamethasone (Dexa) is well-known for its strong anti-inflammatory, immunosuppressive, and anticancer properties. However, its clinical use is often limited by its poor water solubility, poor pharmacokinetics, and high likelihood of systemic side effects. Methods: To address the issues, we tested a combined strategy where our original Drug-Integrating Amphiphilic Nano-Assemblies (DIANAs), a class of self-assembling polymeric nanoparticles designed for controlled drug release, were used to solubilize and deliver dexamethasone palmitate (DexP), a hydrophobic prodrug of dexamethasone. Results: The palmitate chains of the prodrug can form strong van der Waals interactions with the hydrophobic moieties of the PEG-PPS block copolymer used here. In water, this resulted in the self-assembling of stable dexamethasone palmitate–PEG–PPS nanomicelles, termed DexP-nMICs, with a 25 nm average diameter that slowly released Dexa over more than two weeks. Conclusions: Here we demonstrated that DexP-nMICs can carry elevated amounts of Dexa—increasing its solubility in water—prolong circulation in its pharmacologically active form in vivo and provide passive targeting to inflammation sites. The anti-inflammatory efficacy of DexP-nMICs was first confirmed in vitro on stimulated macrophages, demonstrating a significant reduction in cytokine secretion. An allogeneic mouse skin transplant model, used to assess the therapeutic potential of DexP-nMICs in vivo, confirmed its ability to provide graft-targeted delivery and prolong graft survival as compared to the unformulated parent drug. Therefore, DexP-nMICs are a promising candidate for sustained and localized use of anti-inflammatory drugs in cell and tissue transplantations. Full article

Self-assembled nanoparticles formed with amphiphilic block or graft copolymers are being extensively studied for their use in a variety of biological and industrial applications, including targeted drug delivery. This study reports a novel strategy to tune the structure of self-assembled nanoparticles for enhancing the cellular uptake by varying the hydrophilic ratio of amphiphilic graft copolymers. We synthesized poly(aspartic acid) (PAsp) substituted with octadecyl chains (C18) at varying degrees of substitution (DS), ranging from 4.5 to 37.5 mol%, which could form self-assemblies in an aqueous solution. As the DS increased, a morphological transition was observed—from spherical assemblies (DS 4.5 and 9.1) to rod-like (DS 19.0), vesicular (DS 25.7), and lamellar-like structures (DS 37.6). Further, Trans-Activator of Transcription (TAT) as the cell penetrating peptide to the synthesized amphiphilic graft copolymers leads to an enhanced cellular uptake of the biomimetic self-assembly. In particular, the lamellar-like self-assemblies resulted in a 1.3-fold increase of cellular uptake, as compared to the spherical self-assemblies, and a 3.6-fold increase, as compared to the vesicles. Therefore, tuning the structure of poly(aspartic acid)s’ self-assemblies was proven as an effective strategy to enhance the cellular uptake, while minimizing invasive cell damage. This new strategy to tune the morphologies of self-assemblies will serve to improve the cell penetrating activity for targeted drug delivery. Full article

The development of hydrophilic biodegradable polymers is crucial for a range of biomedical applications, including targeted drug delivery and prosthetics. Ring-opening polymerization of substituted ε-caprolactone monomers provides an efficient method for the synthesis of polyesters with tailored properties. In this work, a synthetic approach for the preparation of ester- and morpholinoamido-disubstituted ε-caprolactone monomers was developed. Poorly defined polymers were obtained from the monomers, bearing two ester groups due to the competitive transesterification of the pendant substituents. On the other hand, the disubstituted morpholinoamido-ε-caprolactone was polymerized in a controlled manner by ring-opening polymerization, and amorphous homopolymers with a high glass transition temperature (112 °C) and good solubility in water were obtained. Statistical and block copolymers with the unsubstituted ε-caprolactone were also prepared, and DLS analysis of the amphiphilic block copolymers in water shows the presence of self-assembled particles. These results demonstrate the potential of morpholinoamido-functionalized ε-caprolactone derivatives as building blocks for the development of biodegradable polymeric materials for biomedical applications. Full article

Poly(ε-caprolactone)-b-polysarcosine (PCL-b-PSar) block copolymers (BCPs) emerge as a promising alternative to conventional poly(ε-caprolactone)-b-poly(ethylene oxide) BCPs for biomedical applications, leveraging superior biocompatibility and biodegradability. In this study, we synthesized two series of PCL-b-PSar BCPs with controlled polymerization degrees (DP of PCL: 45/67; DP of PSar: 28–99) and low polydispersity indexes (Đ ≤ 1.1) and systematically investigated their crystallization-driven self-assembly (CDSA) in alcohol solvents (ethanol, n-butanol, and n-hexanol). It was found that the limited solubility of PSar in alcohols resulted in competition between micellization and crystallization during self-assembly of PCL-b-PSar, and thus coexistence of lamellae and spherical micelles. To overcome this morphological heterogeneity, we developed a modified self-seeding method by employing a two-step crystallization strategy (i.e., T_c1 = 33 °C and T_c2 = 8 °C), achieving conversion of micelles into crystals and yielding uniform self-assembled structures. PCL-b-PSar BCPs with short PSar blocks tended to form well-defined two-dimensional lamellar crystals, while those with long PSar blocks induced formation of hierarchical structures in the PCL₄₅ series and polymer aggregation on crystal surfaces in the PCL₆₇ series. Solvent quality notably influenced the self-assembly pathways of PCL₄₅-b-PSar₂₈. Lamellar crystals were formed in ethanol and n-butanol, but micrometer-scale dendritic aggregates were generated in n-hexanol, primarily due to a significant Hansen solubility parameter mismatch. This study elucidated the CDSA mechanism of PCL-b-PSar in alcohols, enabling precise structural control for biomedical applications. Full article

Objectives: Nanosized polymeric micelles (PMs) with an average size of about 80 nm and moderately positive ζ potential, based on an amphiphilic poly(4-methyl-piperazin-1-yl)-propenone)-b-polylactide (PMPP-PLA) block copolymer, were prepared. They were used as platforms for the delivery of bioactive sesquiterpene lactones from Inula helenium L. root extract. Methods: The PMs were characterized with good encapsulation efficiency as a maximum value of 72% was reached at a polymer-to-extract mass ratio of 10:1. The loaded micelles exhibited good colloidal stability. An in vitro release was performed showing a burst release profile. The biocompatibility of the resulting PMs was confirmed by assessing their cytotoxic effect on human keratinocytes in vitro by colorimetric assay and flow cytometry. Results: The systems demonstrated the capability to reduce the biomass of pre-formed Gram-positive and Gram-negative bacterial biofilms. Conclusions: The obtained data clearly determine a trend for a strong combined effect between the PMs and the root extract, distinguishing them with an excellent anti-biofilm potential and prospects for future applications in medical practice. Full article

Delivering of hydrophobic drugs by polymeric nanoparticles is an intensively investigated research and development field worldwide due to the insufficient solubility of many existing and potential new drugs in aqueous media. Among polymeric nanoparticles, micelles of biocompatible amphiphilic block copolymers are among the most promising candidates for solubilization, encapsulation, and delivery of hydrophobic drugs to improve the water solubility and thus the bioavailability of such drugs. In this study, amphiphilic ABA triblock copolymers containing biocompatible hydrophilic hyperbranched (dendritic) polyglycerol (HbPG) outer and hydrophobic poly(tetrahydrofuran) (PTHF) inner segments were synthesized using amine-telechelic PTHF as a macroinitiator for glycidol polymerization. These hyperbranched–linear–hyperbranched block copolymers form nanosized micelles with 15–20 nm diameter above the critical micelle concentration. Coagulation experiments proved high colloidal stability of the aqueous micellar solutions of these block copolymers against temperature changes. The applicability of block copolymers as drug delivery systems was investigated using curcumin, a highly hydrophobic, water-insoluble, natural anti-cancer agent. High and efficient drug solubilization up to more than 3 orders of magnitude to that of the water solubility of curcumin (>1500-fold) is achieved with the HbPG-PTHF-HbPG block copolymer nanomicelles, locating the drug in amorphous form in the inner PTHF core. Outstanding stability of and sustained curcumin release from the drug-loaded block copolymer micelles were observed. The in vitro bioactivity of the curcumin-loaded nanomicelles was investigated on U-87 glioblastoma cell line, and an optimal triblock copolymer composition was found, which showed highly effective cellular uptake and no toxicity. These findings indicate that the HbPG-PTHF-HbPG triblock copolymers are promising candidates for advanced drug solubilization and delivery systems. Full article

Photothermal therapy (PTT) is a promising approach for cancer treatment that has minimal side effects. It locally heats tumors using agents that convert near-infrared (NIR) light energy into heat. We previously reported that the NIR-absorbing hydrophobic diradical-platinum(II) complex PtL₂ (L = 3,5-dibromo-1,2-diiminobenzosemiquinonato radical) can kill cancer cells through its photothermal conversion ability. In this study, we developed PtL₂-loading nanoparticles (PtL₂@RNPs) for the delivery of the complex to tumors based on the enhanced permeability and retention effect using an amphiphilic block copolymer that can scavenge reactive oxygen species. PtL₂@RNPs exhibited particle diameters of 20–30 nm, an encapsulation efficiency exceeding 90%, and loading capacities of up to 12%. Under NIR laser irradiation, PtL₂@RNPs stably generated heat with almost 100% photothermal conversion efficiency. Although the particles were not modified for cancer cell targeting, their uptake by cancer cells was approximately double that by normal cells. PtL₂@RNPs exhibited NIR absorption and effectively killed cancer cells at a low irradiation power (0.15 W). Normal cells treated with PtL₂@RNPs remained largely undamaged under identical irradiation conditions, demonstrating a cancer-cell-specific photothermal killing effect. These findings can provide insights for future basic studies on cancer cells and the development of effective cancer treatment modalities. Full article