Gelatin-based hydrogels as potential biomaterials for colonic delivery of oxaliplatin

Abstract

In present investigation, gelatin-based (AA-co-AMPS) hydrogels were prepared using N, N'-Methylenebisacrylamide (MBA) as a cross-linker and ammonium per sulfate (APS) as an initiator. The successful crosslinking and network formation was confirmed by Fourier transform infrared spectroscopy (FT IR). Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) investigations proved the higher thermal stability and successful entrapment of oxaliplatin (OXP) in the polymeric network. X-ray diffraction (XRD) confirmed the loss in crystallinity of the drug after loading in the hydrogel. Scanning electron microscopy (SEM) revealed the porous surface of the hydrogel. The newly formed hydrogels were responsive to change in pH. The swelling, drug loading and drug release was increased with increase in concentration of acrylic acid (AA) while gelatin and 2-acrylamido 2-methylpronesulfonic acid (AMPS) were found to act inversely. The in-vitro enzymatic degradation study showed that the blank hydrogels were more stable against the blank PBS than the collagenase and lysozyme. MTT-assay proved that the blank hydrogels were cyto-compatible while free OXP as well as OXP-loaded hydrogels showed dose dependent controlled cytotoxicity against Vero, MCF-7 and HCT-116 cell lines. The preliminary safety evaluation and oral tolerability showed that the hydrogel suspension was biocompatible and well tolerable upto 4000 mg/kg of body weight without causing any hematological or histopathological changes in rabbits.

Keywords: Characterization; Gelatin; In-vitro enzymatic degradation; MTT; Oral tolerability; pH-responsive hydrogels.