| Abstrakt: |
Chitosan (Cs) is commonly used in drug and gene delivery systems due to its biocompatibility, biodegradability, cationic properties, and low toxicity. However, its effectiveness is limited by poor solubility and reactivity. [1]. Modifications are often required to enhance its performance. Here, we modified chitosan using poly(N-[3-(dimethylamino) propyl]methacrylamide) (PDMAPMAAm), a weakly cationic polymer with pH-responsive behaviour (pKa - 8.8), biocompatibility and hydrolysis resistance. PDMAPMAAm's attributes make it an excellent candidate for forming stable complexes with anionic biomolecules like DNA and RNA, thereby improving its efficacy as a carrier in gene therapy. Notably, DMAPMAAm surpasses similar monomers such as dimethylamino ethyl methacrylate (DMAEMA) and polyethyleneimine (PEI) in these areas, particularly in terms of reduced cytotoxicity and enhanced control over polymerization[2,3]. In this study, DMAPMAAm was polymerized using reversible addition-fragmentation chain transfer (RAFT) controlled polymerization to produce homopolymers of varying molecular weights. These homopolymers (macroCTA) were then grafted onto chitosan via 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling agents, creating a graft copolymer with tailored molecular characteristics. Chitosan was also degraded into various molecular weights to study its influence on delivery systems. Comprehensive characterization of the synthesized polymers (Cs-g-PDMAPMAAAm, CsgD), including molecular weight determination, buffer capacity measurements, and hemocompatibility tests, confirmed their suitability for biomedical applications. Additionally, the interaction of the polymer with anionic structures was explored by forming nanogels with sodium tripolyphosphate (TPP), simulating its binding potential with phosphate groups present in nucleic acids. Results suggest that both chitosan's backbone chain length and the length of the PDMAPMAAm graft chain affect interaction with TPP. Moreover, the presence of chitosan enhances buffer capacity, with PDMAPMAAm chain length improving this behavior up to a certain point. Hemolysis tests confirmed the non-hemolytic nature of the polymers, though the hemolytic activity of the graft copolymers varied based on chain lengths of Cs and PDMAPMAAm. [ABSTRACT FROM AUTHOR] |
