Fucoidan-Functionalized Nanoparticles for Antimycobacterial Therapy: A Promising Approach against Drug-Resistant...

Tuberculosis remains one of the leading causes of death from infectious diseases. Poly-(isobutyl cyanoacrylate) (PIBCA) polymeric nanoparticles coated with fucoidan were developed as a targeted drug delivery system for rifampicin (RIF) against Mycobacterium tuberculosis (Mtb), including multidrug-resistant strains. The nanoparticles were prepared by anionic emulsion polymerization and characterized for size, surface charge, morphology, stability, and encapsulation efficiency. The formulation exhibited a mean diameter of 400-480 nm, a negative zeta potential (-47.9 ± 1.27 mV), spherical morphology, and colloidal stability for over 30 days, with encapsulation efficiency between 40-50%. In vitro assays demonstrated antimycobacterial activity, with MIC values of 0.412 μg/mL for drug-sensitive strains and 1.238 μg/mL for drug-resistant strains. Synergistic interactions were observed when combined with standard anti-tuberculosis drugs. The nanoparticles showed low cytotoxicity (80-96% cell viability) and concentration- and time-dependent intracellular bactericidal activity in infected macrophages. Cellular uptake studies confirmed efficient internalization, consistent with fucoidan-mediated targeting of macrophage scavenger receptors. These findings highlight fucoidan-coated PIBCA nanoparticles as a promising nanotechnological strategy to enhance rifampicin delivery and efficacy against tuberculosis, particularly in drug-resistant infections.