Chitosan-cellulose hydrogel conjugated with L-histidine and zinc oxide nanoparticles for sustained drug delivery: Kinetics and in-vitro biological studies

Functionalised nanohybrid hydrogel using L-Histidine (HIS) conjugated chitosan, phyto-synthesised zinc oxide nanoparticles (ZNPs) and dialdehyde cellulose (DAC) was formulated as a sustained drug delivery carrier for the polyphenol drugs - Naringenin (NRG), Quercetin (QE) and Curcumin (CUR). A maximum loading efficiency of 90.55 %, 92.84 % and 89.89 %, respectively were optimised for NRG, QE and CUR in the hybrid hydrogel. The maximum drug release was favoured for the optimum drug loading and at pH-5. HIS-chitosan conjugation stabilised the hydrogel and enabled a sustained drug delivery. Drug release kinetics predicted a non-Fickian diffusion-based mechanism along with polymer erosion. Prominent antimicrobial activity against Staphylococcus aureus and Trichophyton rubrum strains were predicted to evolve based on the synergic formulation. Significant biocompatibility towards L929 cells revealed their support for normal cell survival. Anticancer studies towards A431 cells exhibited excellent cytotoxicity with a 15 to 30-fold increase using the hybrid carrier, compared to the free polyphenol drugs.