Hansen Solubility-Guided Design Optimization of Biopolymer-Drug Compatibility for Photodynamically Antimicrobial...

Designing polymeric nanocarriers for hydrophobic therapeutics requires an understanding of polymer-drug interactions and their dependence on polymer molecular weight. Herein, poly(butylene succinate) (PBS) oligomers (αPBS) with tunable molecular weights were prepared via controlled microwave-assisted alcoholysis to investigate the relationships among molecular weight, solubility behavior, and curcumin encapsulation. Experimental solubility mapping revealed substantial deviations between experimentally determined and conventionally predicted Hansen solubility parameters (HSPs) in the oligomeric regime, highlighting the limitations of group-contribution methods for low-molecular-weight polyesters. The PBS oligomer with a M̅n of approximately 2,000 g/mol (αPBS6) exhibited experimental HSP values of δD = 17.0, δP = 7.3, and δH = 7.1 MPa½. Despite borderline-to-unfavorable HSP-derived compatibility with curcumin (RED ≈ 1.04 and χ ≈ 1.21), αPBS6 exhibited high curcumin encapsulation, demonstrating that HSP-derived parameters alone do not directly predict encapsulation efficiency. Curcumin-loaded αPBS nanoparticles (Cur@PBS6) had an average diameter of 232 ± 1.5 nm, a high loading capacity (8.54-9.10%), and good colloidal stability. Their loading capacity exceeded those of commercial PBS (6.36%), PBSA (6.64%), and PLA (2.75%) systems, indicating that molecular-weight modification and nanoparticle formation conditions contribute to curcumin incorporation. Spectroscopic analyses suggested reduced curcumin aggregation following encapsulation, which preserved its photoactivity and promoted reactive oxygen species generation under blue-light irradiation. Moreover, Cur@PBS6-incorporated electrospun poly(lactic acid) fibers exhibited photodynamic antibacterial activity under blue-light irradiation (450 nm, 0.3 W/cm2, 60 min), achieving bacterial killing efficiencies of 94.2% against Escherichia coli and 98.1% against Staphylococcus aureus. These findings demonstrate that experimentally determined HSPs provide a complementary framework for evaluating molecular-weight-dependent polymer-drug interactions, while nanocarrier performance is collectively governed by molecular weight, crystallinity, formulation condition, and other physicochemical factors.