Nanoformulation of Eluxadoline for Targeted Colon Delivery: A Factorial Design Approach for Optimization and Characterization

Abstract

Eluxadoline, a mixed opioid receptor modulator, is an effective treatment for irritable bowel syndrome with diarrhea (IBS-D). However, its systemic metabolism and potential side effects necessitate a targeted drug delivery approach. Colon-specific nanoformulations can enhance localized drug delivery, improve bioavailability, and minimize adverse effects. This study aims to develop and optimize a nanoformulation of eluxadoline for targeted colon delivery using a factorial design approach. The formulation was characterized for its physicochemical properties, in-vitro drug release, and in-vivo therapeutic efficacy.A factorial design was employed to optimize critical formulation parameters, including polymer concentration, surfactant ratio, and stirring speed, to achieve desirable nanoparticle properties. The optimized formulation was characterized for particle size, zeta potential, drug entrapment efficiency, and surface morphology. In-vitro drug release studies were performed under simulated gastrointestinal conditions to evaluate drug release kinetics and colonic targeting efficiency. In-vivo pharmacokinetic and pharmacodynamic evaluations were conducted in IBS-induced animal models to assess bioavailability, drug targeting efficiency, and therapeutic efficacy.The optimized eluxadoline-loaded nanoparticles exhibited a nanoscale particle size, high entrapment efficiency, and controlled drug release at colonic pH. In-vitro and ex-vivo studies confirmed site-specific drug release, while in-vivo pharmacokinetic analysis demonstrated enhanced bioavailability compared to conventional formulations. Pharmacodynamic studies in IBS-induced animal models showed significant symptom relief, improved motility regulation, and enhanced therapeutic efficacy.The factorial design-based nanoformulation of eluxadoline successfully enhanced colon targeting, prolonged drug retention, and improved bioavailability, offering a promising strategy for IBS-D management. Further clinical studies are required to validate its therapeutic potential in human subjects.