Self-Assembly of Alginate-Grafted Penicillanic Acid Derivatives into Antibacterial Micelles for Controlled Drug Delivery

The self-assembly and drug release of amphiphilic polymers are critically controlled by synergistic molecular forces and polymer architecture. Therefore, elucidating the self-assembly behavior of amphiphilic polymers, based on the entropy effect mediated by water molecules, is of significant importance for designing functional nanomicellar carriers. To advance the design of functional nanomicellar carriers, this work innovatively exploited the dual functionality of 6-aminopenicillanic acid (6-APA), a key semisynthetic penicillin intermediate, by grafting it onto alginate via acylation, creating an amphiphilic alginate-grafted penicillanic acid derivative (AM-Alg-APA). This molecular design uniquely integrates inherent antibacterial activity with tunable self-assembly driven by entropy-mediated hydrophobic effects in aqueous systems. The synthesized AM-Alg-APA was able to autonomously form spherical micelles, displaying a hydrodynamic diameter of 568.69 nm with a polydispersity index (PDI) of 0.28 and a zeta potential of −34.8 mV in aqueous solution. This system further demonstrated responsive colloidal behavior to variations in the pH and ionic strength under simulated physiological conditions. Critically, micellar morphologies arose from synergistic intermolecular forces and segmental entropy optimization, enabling efficient encapsulation of hydrophobic triclosan (TCA) via high-shear processing and its controlled release via non-Fickian diffusion. Beyond demonstrating cytocompatibility with MC3T3-E1 cells, the micelles leveraged the grafted 6-APA to confer significant antibacterial activity against S. aureus and E. coli. The multifunctionality, including entropy-regulated self-assembly, stimuli-responsive drug delivery, intrinsic antimicrobial action, and biocompatibility, establishes AM-Alg-APA micelles as innovative platforms for wound-targeted drug delivery in advanced medical dressings.