Enhanced oral bioavailability of megestrol acetate via polymer-hybridized solid lipid nanoparticles using ultrasonic nebulization method

Purpose: Megestrol acetate (MGA) is a BCS class II drug characterized by low solubility and high permeability, resulting in a low oral absorption rate. This study investigates the oral bioavailability of megestrol acetate (MGA) encapsulated in polymer-hybridized solid lipid nanoparticles (PSLNs). Methods: MGA-loaded PSLNs (M-PSLNs) were fabricated by ultrasonic nebulization, and their particle sizes and surface morphology were determined by transmission electron microscopy. Drug loading capacity, thermal behavior, crystalline state, and in vitro release profiles were investigated, and the in vivo oral absorptions of MGA in M-SLNs, M-PSLNs, and micronized MGA in solution were studied using a mouse model and compared. Results: X-ray diffraction showed that crystalline MGA transformed to an amorphous state within PSLNs, and differential scanning calorimetry suggested the maintenance of a stable matrix formation without recrystallization of MGA. In vitro release studies showed that MGA release from SLNs and PSLNs was more rapid than from micronized MGA. A pharmacokinetic evaluation in mice revealed significantly higher MGA oral absorption rates for SLNs and PSLNs than for micronized MGA. Especially, PSLNs showed a 2.87-fold higher oral absorption rate. Notably, PSLNs displayed distinctive double plasma peaks at 0.5- and 2.0-hours of post-administration, indicating a complex absorption profile influenced by formulation factors. Conclusion: Our findings underscore the potential of polymer-hybridized lipid-based nanoparticle formulations in enhancing the oral delivery and pharmacokinetic behavior of MGA, with implications for improved therapeutic outcomes.