HPMCAS-solidified supersaturated baicalin self-nanoemulsifying drug delivery systems: development and anti-colitis...

This study developed a hydroxypropyl methylcellulose acetate succinate (HPMCAS)-functionalized supersaturated self-nanoemulsifying drug delivery system (HPMCAS-SNEDDS@BA) to address the poor solubility and bioavailability of baicalin (BA), a flavonoid with anti-colitis efficacy. The formulation was systematically optimized through solubility screening, emulsification efficiency evaluation, and pseudo-ternary phase diagram analysis. Central composite design-response surface methodology (CCD-RSM) was employed to identify the optimal SNEDDS@BA composition, followed by HPMCAS ratio optimization based on supersaturation maintenance in biorelevant media. Comprehensive characterization included emulsification performance, droplet morphology, solid-state properties, in vitro release, and stability. The optimized formulation (mass ratio: HPMCAS-castor oil-RH40-PEG400-BA = 151.5:20:40:40:1) generated homogeneous, transparent nanoemulsions with spherical droplets, achieving an emulsification time of 48.30 ± 0.74 s, a mean particle size of 47.77 ± 2.32 nm, and a polydispersity index (PDI) of 0.259 ± 0.007. HPMCAS-SNEDDS@BA effectively prevented premature gastric emulsification while enhancing intestinal dissolution rates and sustaining BA supersaturation. Pharmacokinetic studies demonstrated a 5.84-fold improvement in BA bioavailability compared to unmodified formulations. In a dextran sulfate sodium (DSS)-induced colitis model, HPMCAS-SNEDDS@BA outperformed BA suspension and SNEDDS@BA, normalizing colon length, reducing inflammatory cytokines, and restoring mucosal architecture. These findings validate the dual functionality of HPMCAS as a pH-responsive polymer and crystallization inhibitor, enabling targeted intestinal delivery and optimized therapeutic outcomes for ulcerative colitis.