Third Generation Cyclodextrin Graft with Polyurethane Embedded in Hydrogel for a Sustained Drug Release: Complete Shrinkage of Melanoma.

ABSTRACT

An injectable hydrogel-based drug delivery carrier has been developed for long-term drug release by assembling various generations of cyclodextrin (CD) followed by hydrophobic layers to control the drug release for effective cancer treatment. Three generations of CD are designed through urethane linkages using small spacers to create a large hydrophilic core, which is covered with hydrophobic layers of polyurethane through grafting to maintain the hydrophilic hydrophobic balance of the whole superstructure. Drug release becomes sustained from the intricate superstructure following the non-Fickian diffusion process, resulting in massive cancer cell killing as compared to the low killing rate from the pure drug/material arising from its burst release. The superstructure is found to be a good biomaterial, and its drug-loaded conjugate as a carrier is applied to albino mice to treat their tumors, generated through a melanoma cell line. A drug-embedded superstructure is inoculated in an injectable hydrogel and is placed subcutaneously, below the tumor site, which completely healed the melanoma. No side effect was observed, as opposed to the conventional/control system, due to a sustained drug release from the superstructure as evident from histopathological studies of sensitive body organs and biochemical parameters. Thus, a new design of the vehicle heals the melanoma tumor by enhancing the bioavailability of drug and specific interaction without having any side effects as opposed to conventional chemotherapeutic treatment.