Aleksander Forys

This study presents for the first time the synthesis and characterization of superhydrophilic zwitterionic poly(ethyl methacrylate)-b-poly(carboxybetaine methacrylate) (PEMA-b-PCBMA) copolymers. The copolymers prepared using a multi-step Reversible Addition–Fragmentation chain-transfer (RAFT) polymerization method were designed with nearly constant PCBMA length while systematically increasing the length of the hydrophobic PEMA block to study its impact on polymers' self-assembly. Critical concentration and aggregation behavior were investigated across various physiological media, including water, 0.9% NaCl, phosphate buffer saline (PBS), and acidic (pH 3) solutions. The copolymer chains successfully self-assembled into stable, well-defined spherical core–shell micelles in all studied media at critical concentrations. The CMC value clearly depends on the length of hydrophobic block and its fraction in copolymers. Above critical concentration aggregation appears, leading to formation of additional large particles. The environmental factors, i.e. presence of salts and pH, were responsible for the size of particles. After 3 months of storage, no size-changes were observed for the dispersions of micelles in the studied aqueous media formed by copolymers with the lowest hydrophobic fraction while for the copolymer with the highest fraction only large aggregates were present.

Amphiphilic statistical copolymers are valuable synthetic macromolecules for the formation of small, well-defined nanoassemblies able to be utilized as nanocarriers for drug and/or gene delivery applications. In this work, the synthesis of amphiphilic linear statistical copolymers of the poly(benzyl methacrylate-co-dimethylaminoethyl methacrylate) [P(BzMA-co-DMAEMA)] type is described in three different comonomer compositions. Their synthesis was realized through a one-pot reversible addition-fragmentation chain transfer (RAFT) solution polymerization scheme. Further quaternization of the amine groups of DMAEMA with methyl iodide (CH₃I) resulted in cationic amphiphilic statistical copolymers. Macromolecular characterization was performed using size exclusion chromatography (SEC) and spectroscopic techniques (¹H-NMR and ATR-FTIR). The aggregation properties of the copolymers in aqueous media were studied via dynamic light scattering (DLS) and electrophoretic light scattering (ELS). Bimodal size distributions were determined in some cases. The BzMA to DMAEMA ratio determined aggregate size, with the copolymer of lower hydrophobic BzMA content producing smaller nanoparticles. Cryogenic transmission electron microscopy (cryo-TEM) showed the presence of spherical assemblies resulting from aggregation of primary micelles in the case of higher BzMA content. The copolymer aggregates experience dissociation at high salt concentration, and the pH-responsiveness of the amine precursors results in the formation of multifunctional potential nanocarriers.

Amphiphilic copolymers represent a primary class of stabilizers for lipid–polymer hybrid nanoparticles. Among them, lyotropic liquid crystalline nanoparticles (LLCNPs) have some significant advantages, such as controlled release, targeted delivery and protection of active compounds, towards their use as potential carriers of active substances or drugs. The aim of this work is to study a series of linear amphiphilic block copolymers for stabilization of glyceryl monooleate [1-(cis-9-octadecenoyl)-rac-glycerol]-based lipid–polymer hybrid nanoparticles. For this purpose, poly(ethylene glycol)-b-poly(benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate), poly(ethylene glycol)-b-poly(9,9-dimethyl-2,4,8,10-tetraoxaspiro[5.5] undecan-3-one), and poly(ethylene glycol)-b-poly(trimethylene carbonate) were synthesized using anionic ring opening polymerization and poly[oligo(ethylene glycol) methacrylate]-b-poly(ethyl methacrylate) was synthesized by atom transfer radical polymerization. The chemical structures of copolymers were confirmed by ¹H-NMR, while the molar masses were determined by SEC measurements. Lipid–polymer nanosystems were prepared by the top-down method. Their physicochemical and morphological characteristics were assessed through dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), fast Fourier transform (FFT) analysis and microcalorimetry (mDSC). Varying the molar ratios of GMO to copolymers resulted in nanoparticles with different sizes and internal organization, with these properties being influenced by the type of hydrophobic block used in the copolymer, as can be expected and observed for other LLCNPs stabilized with amphiphilic block copolymers. This study introduces a broader group of amphiphilic polymeric stabilizers for the development of LLCNPs and highlights how variations in copolymer composition affect the structural characteristics and properties of emerging nanosystems.

Background/Objectives: Lyotropic liquid crystalline nanoparticles are promising drug delivery nanocarriers, exhibiting significant technological advantages, such as their extended internal morphology. In this study, cationic non-lamellar lyotropic–lipidic liquid crystalline nanoparticles were formulated by phytantriol lipid. Methods: The poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) block copolymer carrying tri-phenyl-phosphine cations (TPP-QPDMAEMA-b-PLMA), was employed as a stabilizer co-assisted by other polymeric guests. The exact qualitative and quantitative formulation of the systems was investigated. Their physicochemical profile was depicted from a variety of light scattering techniques, while their microenvironmental parameters were determined by fluorescence spectroscopy using adequate probe molecules. The effect of environmental conditions was monitored, confirming stimuli-responsiveness properties. Their morphology was illustrated by cryo-TEM, revealing expanded internal assemblies. Resveratrol was incorporated into the nanoparticles and the entrapment efficiency was calculated. Results: Their properties were found to be dependent on the formulation characteristics, such as the lipid used, as well as the architecture of the polymeric stabilizer, also being found to be stealth toward proteins, exhibiting stimuli responsiveness and high entrapment efficiency. Conclusions: The studied liquid crystalline nanoparticles, being stimuli-responsive, with high cationic potential, high loading capacity and showing intriguing 3D structures, are suitable for pharmaceutical applications.

Background/Objectives: The study describes the elaboration and evaluation of thermosensitive niosomes intended for the systemic application of daunorubicin hydrochloride. The attained stimulus sensitivity would determine the release of the chemotherapeutic predominantly at the target site, which ensures a higher drug concentration and leads to reduced systemic toxicity. The latter is highly beneficial, as the anthracycline antibiotic is known for its dose-dependent cardiotoxic effects. Methods: Conventional and copolymer-modified niosomes were prepared via thin-film hydration and the transmembrane ammonium gradient method, allowing us to assess the impacts of copolymer type-DHP-PiPOX (1,3-dihexadecyl-propane-2-ol-poly(2-isopropyl-2-oxazoline)) or DHP-PETEGA (1,3-dihexadecyl-propane-2-ol-poly(ethoxytriethylene glycol acrylate)) and their concentrations (0.5, 1, and 2.5 mol%), as well as the method of preparation, on the main physicochemical properties of the vesicles. Niosomes were characterized in terms of their size, polydispersity index (PDI), zeta potential, entrapment efficiency, morphology, and drug release properties. Thermosensitivity was evaluated by fluorescence studies, and the antiproliferative activity of optimized formulations was assessed against the acute myelocyte leukemia-derived HL-60 cell line. Results: Daunorubicin-loaded niosomes modified with DHP-PiPOX and DHP-PETEGA at 2.5 mol% exhibited suitable physicochemical properties for systemic application, with sizes below 200 nm (155 and 158 nm respectively), low PDI values of 0.25 and 0.29, spherical morphology, and high daunorubicin entrapment efficiency (68.6 and 66.5% respectively). The vesicles showed temperature-dependent drug release properties and superior antiproliferative activity compared to the free daunorubicin (IC₅₀ values of 6.91 and 8.54 vs. 12.14). Conclusions: The obtained results indicate that the developed thermosensitive nanovesicles may serve as a suitable drug delivery system for the systemic application of daunorubicin hydrochloride.

This study explored the structural modification of bacterial cellulose (BC) through enzymatic hydrolysis using varying cellulase activities and substrate concentrations. Optimal hydrolysis conditions (50 U/g of BC; 20 g/L of BC) were established to balance recovery and homogeneity (yielding BNC1). Hydrolysis was further combined with nonthermal plasma by suspending BC into plasma-activated water (PAW) prior to hydrolysis (BNC2). In another approach, BC suspensions were pretreated using a plasma bubble reactor followed by hydrolysis (BNC3). BNC1 and BNC2 yields were similar (∼50%), suggesting that PAW regulated the pH during hydrolysis. BNC3 yield was significantly higher (78%) compared to BNC1, indicating that the generated radicals promoted chain modifications while minimizing glucose/cellobiose release. That dual approach led to BC defibrillation, as revealed by AFM/cryo-TEM. The reduction in melting temperature observed was correlated with a crystallinity drop. Dual enzymatic and plasma-assisted strategies offer novel-intriguing avenues to fine-tune the properties of cellulose nanocomposites for sustainable applications.