Copolymer Composition and Nanoparticle Configuration Enhance in vitro Drug Release Behavior of Poorly Water-soluble Progesterone for Oral Formulations

摘要

Hypothesis: Developing oral formulations to enable effective release of poorly water-soluble drugs like progesterone is a major challenge in pharmaceutics. Coaxial electrospray can generate drug-loaded nanoparticles of strategic compositions and configurations to enhance physiological dissolution and bioavailability of poorly water-soluble drug progesterone. Experiments: Six formulations comprising nanoparticles encapsulating progesterone in different poly(lactide-co-glycolide) (PLGA) matrix configurations and compositions were fabricated and characterized in terms of morphology, molecular crystallinity, drug encapsulation efficiency and release behavior. Findings: A protocol of fabrication conditions to achieve 100% drug encapsulation efficiency in nanoparticles was developed. Scanning electron microscopy shows smooth and spherical morphology of 472.1± 54.8 to 588.0± 92.1 nm in diameter. Multiphoton Airyscan super-resolution confocal microscopy revealed core-shell nanoparticle configuration. Fourier transform infrared spectroscopy confirmed presence of PLGA and progesterone in all formulations. Diffractometry indicated amorphous state of the encapsulated drug. UV-vis spectroscopy showed drug release increased with hydrophilic copolymer glycolide ratio while core-shell formulations with progesterone co-dissolved in PLGA core exhibited enhanced release over five hours at 79.9± 1.4% and 70.7± 3.5% for LA:GA 50:50 and 75:25 in comparison with pure progesterone without polymer matrix in the core at 67.0± 1.7% and 57.5± 2.8%, respectively. Computational modeling showed good agreement with the experimental drug release behavior in vitro.