From Monomer to Therapeutic Nanocarrier: Design, Characterization, and Anticancer Evaluation of Poly (Alpha-Lipoic Acid) Nanoparticles

Abstract

Nanotechnology has revolutionized drug delivery by enhancing therapeutic agent targeting, controlled release, and pharmacokinetics. Poly(α-lipoic acid) (PαLA), a biodegradable and redox-responsive polymer derived from α-lipoic acid (αLA), presents a promising nanocarrier system due to its biocompatibility and structural versatility. In this study, PαLA was synthesized via thermal ring-opening polymerization and subsequently formulated into nanoparticles (PαLA-NPs) using a modified nanoprecipitation method. The polymer and nanoparticles were characterized using UV-Vis spectroscopy, FTIR, dynamic light scattering(DLS), and transmission electron microscopy (TEM). The nanoparticles exhibited a spherical morphology with an average size of 70.98 nm, a polydispersity index (PDI) of 0.192, and a zeta potential of -20.4 mV, indicating good colloidal stability. Cytotoxicity assessment via MTT assay revealed that PαLA-NPs induced concentration-dependent cytotoxicity in human colorectal adenocarcinoma (HCT-116) cells while maintaining high biocompatibility with normal fibroblasts (BJ-1). Notably, at 50 µg/mL, PαLA-NPs reduced HCT-116 viability to ~65% but preserved over 90% viability in BJ-1 cells, demonstrating selective anticancer potential. These findings suggest that PαLA-NPs are a promising nanocarrier system for targeted cancer therapy with minimal off-target toxicity