Synthesis of N-acetylcysteine functionalized cholic acid based triarmed poly DL-Lactide and encapsulation of gold nanoparticles: Studies on the antimicrobial activity and biocompatibility for drug delivery applications

• Published in: International journal of biological macromolecules 2024-11, Vol.279 (Pt 1), p.135085, Article 135085
• Main Authors: Ezhumalai, Nishanthi, Nanthagopal, Manivannan, Kasthuri, Jayapalan, Rajendiran, Nagappan
• Format: Article
• Language: English
• Subjects: Antimicrobial; Drug delivery; Gold nanoparticles; N-acetylcysteine conjugated cholic acid; Reverse polymeric micelles
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.135085

Cholic acid based biodegradable reverse polymeric micelles have been widely utilized as preclinically suitable drug delivery system for poorly water-soluble drugs. In this report, we developed N-acetylcysteine functionalized cholic acid based triarmed poly (Dl-lactide) (ACyCA-triarmed (DLL)n as reversed polymeric micelles for drug delivery studies. ACyCA was synthesized via thiol-yne click reaction and subsequently used as an initiator for the synthesis of ACyCA-triarmed (DLL)n through ring opening polymerization (ROP) using Sn (Oct)2 as a catalyst. The synthesized ACyCA-triarmed (DLL)n was characterized using GPC, FT-IR, 1H NMR, 13C NMR, spectrofluorometer, HR-TEM, DSC, TGA, XRD, DLS, and zeta potential techniques. The reverse critical micellar concentration of the polymer was determined to be 1.99 mg/mL using a spectrofluorometer. The synthesized reverse micelles (RMs) were utilized as a reducing and capping agent for the preparation of AuNPs under sunlight exposure. The formed AuNPs exhibited spherical in shape with an average size of ∼ 23.4 nm and Dh was found to be 86.8 ± 1.3 nm as evidenced by the TEM and DLS analysis. Furthermore, the antimicrobial activity, hemolytic activity, anti-oxidant activity, and in-vitro drug release studies were examined for the RMs-AuNPs and compared with RMs. The hydrophobic nature of RMs and RMs-AuNPs had better haemocompatibility at above the reversed CMC. The antioxidant activity RMs-AuNPs showed better inhibitory effect in a dose-dependent manner as compared to RMs. The RMs-AuNPs formulation act as reservoir for solubilization of hydrophobic doxorubicin (Dox.HCl) drugs and can be used as therapeutic platform for slow and sustained release of drugs in biological medium. [Display omitted]