Enzymatic and Oxidative Modification of Maize Starch Microparticles for Controlled Release and Antibacterial Activity of Polymyxin B Peptide

Antibiotic resistance represents a pressing global health challenge, with polymyxins serving as one of the last lines of defense against multidrug-resistant Gram-negative pathogens. Among them, polymyxin B (PMB) has gained renewed attention; however, its clinical use is limited by systemic toxicity. This study developed porous maize starch microparticles with tunable structure and surface chemistry to modulate PMB loading and release. Porous normal maize starch (NMS) and high-amylose maize starch (HAMS) were prepared by enzymatic treatment and modified by 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation to introduce anionic carboxyl groups for PMB binding. Structural characterization revealed distinct pore morphology and lamellar organization in NMS- and HAMS-derived microparticles, while oxidation increased surface charge without disrupting granular integrity. TEMPO oxidation substantially enhanced PMB loading, suggesting that electrostatic interactions between PMB and oxidized starch contributed to adsorption. In an enzyme-assisted in vitro release model, oxidized porous starches exhibited biphasic profiles, with an initial rapid release followed by a plateau, indicating heterogeneous PMB binding. Oxidized porous NMS (NMS-P-T) and oxidized porous HAMS (HAMS-P-T) showed more sustained PMB release than non-oxidized particles. PMB-loaded HAMS-P-T maintained prolonged antibacterial activity against Escherichia coli in vitro relative to NMS-based matrices. These findings demonstrate that structural modification and surface-charge influence PMB loading and release behavior in starch microparticles, enabling the design of starch-based antimicrobial peptide delivery systems.