Poly(vinyl alcohol) and Functionalized Ionic Liquid-Based Smart Hydrogels for Doxorubicin Release.

Abstract

Limitations associated with the traditional cancer therapies prompt the scientific community to develop effective, safer, smarter, and targeted drug carriers that improve the efficiency of the drug carrier, reduce the adverse effects of the drug on the healthy cells, and help in preventing the cancer recurrences. This research aims to design a stimuli-responsive, self-healable, adhesive, and injectable polymeric hydrogel with an ester-functionalized ionic liquid as one of the additives to improve the efficiency of the anticancer drug in encapsulation and localized delivery. The designed polymeric hydrogel responds to intracellular biological stimuli (e.g., acidic pH of cancerous cells and temperature), changes the morphology through changing the shape and size of the gelator within the hydrogel matrix, and releases encapsulated doxorubicin (DOX) at the tumor site efficiently. Molecular interactions, gel morphology, and mechanical strength of the hydrogel were characterized through various analytical techniques, including small-angle neutron scattering. Adhesive properties of the polymeric hydrogel were measured by lap-shear strength tests and the biocompatibility and cellular drug uptake study on human breast cancer (MCF-7) and human cervical carcinoma cells (HeLa). The in vitro cytotoxicity and drug release study showed that the hybrid hydrogel is more effective at killing the cancerous cells, and the targeted release of DOX occurred at intracellular acidic pH. The polymeric hydrogel provides an efficient therapeutic approach for the encapsulation and release of the drug. Overall, the study offers a proof of concept to test the feasibility of the hydrogel system whether the hydrogel formulation helped or hindered the total cellular DOX trafficking.