Structural modulation of PCL and PCL–PLGA nanoparticles governs physicochemical properties and drug release kinetics

Abstract

The semi-crystalline and hydrophobic nature of poly(ε-caprolactone) (PCL) can limit drug release from polymeric nanoparticles (NPs). Strategies such as PCL amorphization and PCL–poly(lactic-co-glycolic acid) (PLGA) blending modify polymer structural organization, but the extent to which these approaches influence drug release remains insufficiently understood. This study compared these strategies and examined how structural organization affects drug release. Irinotecan hydrochloride–loaded PCL and PCL–PLGA NPs were prepared by double-emulsion solvent evaporation and characterized for morphology, crystallinity, thermal properties, stability, and in vitro drug release. Release mechanisms were evaluated using zero-order, first-order, Higuchi, and Korsmeyer–Peppas models. Thermal analysis demonstrated reduced crystallinity through melting point depression, disappearance of the drug melting peak, and drug dispersion within the polymer matrix. A single glass transition temperature confirmed blend miscibility. Incorporation of PLGA enhanced drug release through increased hydrophilicity and reduced crystallinity, while both formulations exhibited sustained diffusion-controlled release. Stability improved under mildly acidic and tissue culture conditions compared with phosphate-buffered saline. Modifying polymer structural organization through PCL amorphization or PCL–PLGA blending influenced crystallinity, thermal behavior, and drug release. These findings provide insight into the relationship between polymer structural organization and sustained drug release, supporting rational design of polymeric drug delivery systems.