Design and synthesis of poly (ethylene glycol) methyl ether-block-polycaprolactone grafted chitosan injectable hydrogels for curcumin delivery

Abstract

Injectable hydrogels serve as an alternative solution for drug delivery in various biomedical applications. Typically, these hydrogels are based on stimuli-responsive polymers capable of response to changes in the physical or chemical properties of the surrounding environment, such as alterations in temperature or pH levels. In this study, chitosan-graft-(methoxy poly(ethylene glycol)-block-polycaprolactone) injectable hydrogels were synthesized and loaded with different concentrations of curcumin. As the curcumin concentration increased, there was a corresponding rise in curcumin loading content within these hydrogels. Although the encapsulation efficiency showed a slight decrease with higher curcumin concentrations, it consistently remained impressively high, exceeding 90% for all formulations. Such hydrogels demonstrated a sustained release manner for curcumin. The release profiles followed the Korsmeyer-Peppas and zero-order kinetic release models which suggested that the release of curcumin from hydrogel primarily occurred through drug diffusion and the gradual erosion of the self-assembled polymeric networks. Additionally, the size of the released curcumin, existing as core-shell nanoparticles, depends on the loading concentration. Fluorescence spectroscopy and thermodynamic analysis were employed to analyze the interactions between curcumin and the copolymers. The results suggested that van der Waals interactions and hydrogen bonds played pivotal roles in binding curcumin to the copolymers. Additionally, In vitro cytotoxicity studies showed that exposure to the curcumin-encapsulated nanoparticles significantly decreased the viability of the cervical cancer HeLa cell line.