Preparation of natural polymer-based hydrogels for oral delivery of anti-malarial drug: <i>in vitro</i> and cytotoxicity evaluation

The current investigation involved the fabrication of gelatin-based hydrogels for controlled delivery of quinine. Hence, pH-responsive and biocompatible hydrogels were developed using natural polymer gelatin and synthetic monomer acrylic acid. The drug-loaded hydrogels indicated a new carrier system, which was confirmed by various physicochemical characterizations, including FTIR, TGA, DSC, and XRD, whereas SEM revealed the morphology of unloaded and drug-loaded hydrogels, respectively. Similarly, sol-gel and porosity studies were conducted to assess the soluble, insoluble, and fluid penetration across the prepared network. A significant increase in gelation, whereas a decline in sol fraction was detected with high hydrogel contents. Unlike gel fraction, a decline was observed with high integration of gelatin and <i>N</i>',<i>N</i>'-methylene bisacrylamide, while acrylic acid showed the same effects as gel fraction on the porosity of the polymeric matrix. Swelling and drug release investigations confirmed the pH-dependent release of quinine at various simulated pH values of 1.2, 4.6, and 7.4, respectively. Both swelling and drug release showed a high swelling index and release of the drug from the fabricated hydrogel at higher pH values compared to lower pH values. Similarly, drug loading was conducted by a swelling and diffusion approach. The effects of acrylic acid, gelatin, and <i>N</i>',<i>N</i>'-methylene bisacrylamide were the same on swelling, drug loading, and release as porosity. The biodegradation study revealed that high polymer, monomer, and crosslinker concentrations led to a slow hydrogel degradation. Furthermore, the developed matrix was subjected to cytotoxicity and cell viability studies on mouse fibroblast L929 cells, which indicated safe utilization of polymeric hydrogels with negligible toxicity. Hence, the strategy of preparing pH-responsive hydrogels of gelatin facilitates the controlled delivery of quinine for a prolonged time in order to overcome the challenges of quinine generated after its multiple intakes.