Enhancing solubility and oral bioavailability of rosuvastatin through interpenetrating polymer network (IPN) nanogels: Fabrication, characterization, and in-vivo efficacy assessment

Abstract

Rosuvastatin (RST) exhibits low aqueous solubility, presenting a challenge for its effective oral administration. The objective of this study is to improve the solubility of RST through the creation and assessment of interpenetrating polymer network (IPN) nanogels. The nanogels were produced via a free radical polymerization method, where hydrophilic polymers β-cyclodextrin (β-CD) and Poloxamer-407 (P407) were combined with the monomer 2-acrylamido-2-methylpropane sulfonic acid (AMPS). Comprehensive characterization of the nanogels included drug loading efficiency, solubility studies, zeta sizer measurements, sol-gel analysis, Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), swelling studies, and in-vitro release analysis. Oral toxicity experiments were performed to verify the safety of the β-CD/Poloxamer-407-co-poly (AMPS) IPN nanogels when taken by mouth. The scanning electron microscopy (SEM) investigation unveiled a network structure characterised by porosity and sponginess. The thermal stability and complex synthesis of the nanogel components were validated by the FTIR, TGA, and DSC spectra. X-ray diffraction (XRD) analysis indicated a reduction in the crystallinity of RST within the nanogel matrices. The optimized nanogels formulation demonstrated a particle size of 185.71 ± 1.03 nm. Comparative studies with a reference product highlighted significant enhancements in drug solubility and release characteristics attributed to the fabricated nanogels. Toxicity assessments confirmed the non-toxic nature of the nanogels, supporting their biocompatibility. In-vivo studies using hyperlipidemic animal models validated the anti-hyperlipidemic efficacy of the developed nanogels. The nanogels' biocompatibility, high solubilization capacity, improved dissolution profile, rapid production process, and superior physicochemical properties underscore their potential as an effective oral delivery system for lipophilic drugs.