Lipid-Based Formulations Enhance the Apparent Intestinal Permeability of BGP-15: Physicochemical Characterization and Caco-2 Transport Studies.

BGP-15 is a pleiotropic small molecule with cytoprotective, anti-inflammatory, and insulin-sensitizing effects, but its biopharmaceutical properties remain insufficiently characterized. This study investigated its pH-dependent distribution, Caco-2 permeability, and the effect of lipid-based formulations on apparent absorptive transport. The octanol-buffer distribution coefficient was determined over pH 1.5-10.5. BGP-15-loaded liposomes (LS) and solid lipid particles (SLP) were characterized for particle size, polydispersity, zeta potential, drug loading, and encapsulation efficiency, and selected formulations were evaluated in bidirectional Caco-2 transport studies. BGP-15 remained predominantly hydrophilic under acidic and near-neutral conditions and showed low apical-to-basolateral permeability as a free compound (1.40 × 10⁻⁶ cm/s), with marked directional transport asymmetry. LS3 and SLP3 significantly increased apical-to-basolateral permeability to 2.06 × 10⁻⁵ and 1.32 × 10⁻⁵ cm/s, respectively, while reducing the calculated efflux ratios to 1.18 and 1.30. ATPase assays showed no consistent concentration-dependent interaction with MDR1, ABCG2, or MRP2. These findings demonstrate a formulation-associated increase in the apparent absorptive transport of BGP-15 and support further investigation of lipid-based delivery approaches.