The development of efficient and biocompatible polymeric vectors remains a cornerstone of successful gene therapy. In this study, we developed a versatile polymeric platform for nucleic acid delivery by synthesizing a series of cationic block copolymers based on polyaspartamide or polyglutamide backbones and polyethylene glycol (PEG) segments. Block copolymer precursors were synthesized via ring-opening polymerization. The degrees of polymerization were confirmed via ¹H NMR spectroscopy, followed by functionalization with diethylenetriamine, spermine, or spermidine. Cytotoxicity was evaluated using the WST-1 assay in HEK293 and SH-SY5Y cells. Cytotoxicity profiling identified N₃-PEG₁₁₄-b-pAsp(DET)₆₂ as the least cytotoxic polymer among the tested derivatives in both cell lines. The polyplexes enhanced reporter gene expression compared with naked plasmid DNA, and an N/P ratio of 15 was selected for subsequent comparative experiments. In SH-SY5Y neuroblastoma cells, the material obtained following the dopamine-modification procedure exhibited a 1.78-fold increase in reporter fluorescence and a 1.75-fold increase in the percentage of GFP-positive cells compared with the corresponding unmodified formulation. These findings establish the engineered block copolymers as highly adaptable, low-toxicity, and efficient candidates for targeted nucleic acid delivery and support the potential of dopamine functionalization for enhancing delivery to dopamine-receptor-expressing cells.

Background: Despite extensive development of liposomal antibiotics, the structural determinants governing their stability, release, and biological activity remain poorly understood. This study investigated how the cholesterol content and drug-to-lipid ratio affect membrane organization and thereby determine the physicochemical and biological properties of linezolid-loaded liposomes. Methods: Nine liposomal formulations, varying in their cholesterol content (10–30 wt%) and drug-to-lipid ratios (1–5%), were prepared by thin-film hydration. Membrane organization was analyzed by ATR-FTIR spectroscopy and principal component analysis. Liposomes were further characterized by particle size, ζ-potential, encapsulation efficiency, storage stability, in vitro release in phosphate buffer with and without bovine serum albumin, antibacterial activity against B. subtilis, and antimycobacterial activity in an ex vivo PBMC-derived Mycobacterium tuberculosis granuloma model. Results: The cholesterol content and drug-to-lipid ratio markedly altered membrane interfacial organization, particularly the hydration of the carbonyl and phosphate regions. These structural changes correlated with differences in storage stability, protein-responsive release, and antibacterial activity. Functional behavior was non-monotonic, as 30-L showed the highest overall storage stability, while the apparent release depended jointly on the cholesterol content, drug loading, and medium. BSA altered the composition-dependent release pattern instead of producing a uniform effect. In the exploratory granuloma model, the formulations 10-S, 10-L, and 30-M reduced M. tuberculosis CFU by >99%, whereas free linezolid produced approximately 60% inhibition. Conclusions: Membrane interfacial organization is a key determinant of the functional performance of liposomal linezolid, establishing a structure–property–function relationship that provides a mechanistic basis for the rational design of liposomal antibiotic delivery systems for tuberculosis therapy.

Iron deficiency anemia continues to pose a significant global health burden, necessitating the development of improved therapeutic delivery systems. This study investigates novel composite materials composed of organosilicon hydrogels and cross-linked sulfobutyl ether beta-cyclodextrin (SBECD) nanoparticles for the oral delivery of iron compounds. Two types of cross-linked SBECD nanoparticles were synthesized using 1,6-hexamethylene diisocyanate. These nanoparticles were characterized by DLS, NTA, and FTIR and possess size around 200–300 nm and negative zeta-potential around −35 mV with molecular weight 150–200 kDa. Various hydrogel matrices, including plain PMSSO hydrogels and modified versions with amino groups or silicate cross-links, are also described. The hydrogels were evaluated for their iron sorption capacity (up to 44% loading efficiency) and release kinetics for 3 h. The results demonstrate that cross-linked SBECD nanoparticles significantly enhance iron sorption and provide sustained release under simulated physiological conditions. Mathematical modeling indicated that the Higuchi model best describes the iron release kinetics. The findings suggest that the proposed composite materials hold considerable promise for the treatment of iron deficiency anemia, offering an innovative approach to enhance therapeutic efficacy and minimize adverse effects.