Overcoming Bioavailability Barriers: Optimized Hybrid Nanocarrier System to Amplify Berberine Absorption via Peyer's...

Berberine, an isoquinoline alkaloid, is a compound of interest due to its structural diversity and wide range of biological activities; however, its pharmacological effects are significantly limited by poor intestinal absorption. In this study, a novel formulation approach was employed to improve the bioavailability of berberine by formulating lipid-polymer hybrid nanoparticles (BER-LPHN) using a modified nanoprecipitation method. The formulation was optimized using a 3² full factorial design, incorporating Phospholipon 90 H as the lipid and Gantrez as the hydrophilic polymer. The optimized BER-LPHN exhibited a nanosize of 250-350 nm and a zeta potential of -25.00 ± 2.2 mV, with notably high drug loading (~ 87%). TEM analysis revealed the spherical morphology of the BER-LPHN, with the lipid coat surrounding the polymeric matrix, which facilitated controlled drug release from the polymeric core in vitro, resulting in an 18-fold increase in the oral bioavailability of berberine. In-vivo studies using fluorescently labeled nanoparticles demonstrated a significant concentration of BER-LPHN near the villi boundary and significant uptake by Peyer's patches. Confocal microscopy further confirmed the lymphatic uptake of BER-LPHN through M cells of Peyer's patches, suggesting that the formulated nanoparticles have the potential to enhance berberine's bioavailability by boosting permeability in the intestine via lymph transport.