Development And Optimization Of Baicalin Nanoparticle Loaded Oral Hydrogel For Colon-Targeted Therapy In Inflammatory Bowel Disease

Abstract

Objectives: To develop and optimize baicalin-loaded Eudragit S100-coated PLGA nanoparticles using Soluplus® as a novel steric stabilizer and incorporate the optimized batch into a Carbopol 974P NF oral hydrogel for pH-responsive colon-targeted delivery in inflammatory bowel disease, addressing the biopharmaceutical limitations of baicalin as a BCS Class IV drug. Methods: Nine nanoparticle batches (NF1–NF9) were prepared by nanoprecipitation and optimized using a 3² full factorial design with PLGA concentration (X₁) and Soluplus® concentration (X₂) as independent variables, evaluating particle size and entrapment efficiency as responses. The optimized batch was incorporated into four Carbopol 974P NF hydrogel batches (G1–G4) and evaluated for physicochemical properties, mucoadhesion, ex vivo colonic permeation, and accelerated stability. Results: The quadratic models demonstrated excellent predictability (R² = 0.9992 and 0.9995). Batch NF8 (PLGA 1.5% w/v, Soluplus® 1.0% w/v) was selected as optimized based on desirability score of 1.000, particle size of 184.6 nm, PDI of 0.218, zeta potential of −27.6 mV, and entrapment efficiency of 86.7%, with sustained colonic release of 81.62% at 12 hours. Hydrogel batch G3 demonstrated highest steady-state flux of 107.44 µg/cm²/hr and 12-hour cumulative permeation of 68.24%. Accelerated stability studies confirmed formulation integrity over three months. Conclusion: The developed nanoparticle-loaded oral hydrogel offers pH-responsive colon targeting, strong mucoadhesion, and sustained drug release, presenting significant clinical potential for localized IBD therapy with reduced systemic toxicity and improved patient compliance, warranting further in vivo validation.