Crosslinked PVA-g-poly(AMPS) Nanogels for Enhanced Solubility and Dissolution of Ticagrelor: Synthesis, Characterization, and Toxicity Evaluation.

ABSTRACT

In this study, we synthesized PVA-g-poly(AMPS) nanogels with the aim of enhancing the solubility and dissolution of ticagrelor (TGR). Ticagrelor, a noncompetitive, reversible P2Y12 receptor antagonist, is prescribed to treat acute coronary syndrome. Ticagrelor has restricted oral bioavailability (≈36%) because of its poor solubility and permeability. The free radical polymerization methodology was employed to synthesize nanogels with varied concentrations of poly(vinyl alcohol) (polymer), 2-acrylamido-2-methylpropanesulfonic acid (monomer), and N,N-methylene bis(acrylamide) (crosslinker). The prepared nanogels were analyzed by swelling studies, % drug entrapment efficiency (DEE), solubility studies, in vitro drug release studies, zeta sizer, Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). The optimized formulation (PA5) revealed a particle size of 45.86 nm, with a polydispersity index (PDI) of 0.41 and a %DEE of 85.1%. FTIR spectroscopy, XRD, and SEM confirmed the formation of crosslinked nanogels with amorphous and porous structures, and TGA/DSC proved their thermal stability. In vitro dissolution studies showed 99.91% drug release, and the ticagrelor solubility from the synthesized formulations was significantly improved up to 8.2-fold. All formulations followed the Korsmeyer-Peppas model with the Fickian diffusion as the release mechanism. The toxicity studies carried out on rats and the MTT assay on the Caco-2 cell line validated the biocompatibility of the nanogel formulations. The outcomes of the current study led to the conclusion that the PVA-g-poly(AMPS) nanogels synthesized by us could be used as dedicated pharmaceutical delivery systems to achieve enhanced solubility and dissolution of ticagrelor.