Nano Engineered Chitosan-Based Delivery System for Vonoprazan Fumarate for Enhanced Bioavailability: Fabrication and Evaluation

Purpose: The main purpose of the present study was to explore chitosan as a polymeric material for the preparation of vonoprazan nanoparticles intended for use as a delivery system for acid-related diseases. Methods: Vonoprazan-loaded chitosan nanoparticles were formulated using the ionotropic gelation method and characterized in terms of size, zeta potential, polydispersity index, drug entrapment efficiency (EE), FTIR, XRD, Thermal analysis, SEM, in vitro release study at two different pH levels, and drug release kinetics. Acute oral toxicity was assessed to evaluate safety and pharmacokinetic studies were performed to determine bioavailability. Results: The optimized formulation VCHNP4 demonstrated a mean particle size of 496.5± 1.19 nm, a zeta potential of 25.4± 3.07 mV, a polydispersity index of 0.474± 1.97, and an entrapment efficiency of 78.09± 0.41. Surface morphology studies revealed a spherical shape with inclusions of drug-loaded chitosan nanoparticles. Thermal stability was improved, as observed by thermal analysis, and PXRD confirmed the amorphous state of the drug. Saturation solubility testing indicated significantly enhanced solubility of the drug and exhibited pH-dependent drug release, with higher release at pH 1.2 compared to pH 6.8, following the Korsmeyer-Peppas model. Acute oral toxicity studies showed no major differences in the clinical parameters between the control and treatment groups. In vivo pharmacokinetics showed that VCHNPs achieved superior Cmax (307 ± 0.61 ng/mL) compared to VPZ (41 ± 1.01 ng/mL) (p < 0.05). Conclusions: This study showed that mucoadhesive polymeric nanoparticles of vonoprazan significantly enhanced solubility, pH-dependent release, and improved mucoadhesion, making it a promising approach to improve the oral bioavailability of drugs with poor water solubility. Keywords: chitosan, vonoprazan fumarate, peptic ulcer disease, solubility, pharmacokinetic study, bioavailability, toxicity studies