Defining cisplatin incorporation properties in thermosensitive injectable biodegradable hydrogel for sustained delivery and enhanced cytotoxicity

Abstract

Injectable thermoreversible chitosan (CS)/β-glycerophosphate (β-GP) hydrogels were developed for prolonged localized delivery of cisplatin (Cis). The effects of formulation variables on the thermoreversible hydrogels preparation as well as the impact of drug incorporation method on Cis release were studied. Antitumor activity of Cis CS/β-GP thermoreversible hydrogels were evaluated against HCT-116 human colorectal cancer cells and MCF-7 human breast cancer cells. Incorporation of Cis to CS solution adjusted at pH 6.2 prior to hydrogel preparation deemed necessary to achieve a sustained release up to 4 days. Cis loaded CS/β-GP thermoreversible hydrogels showed enhanced antitumor activity with about 1.2 fold and 2.05 fold that of Cis solution against HCT-116 cancer cells and MCF-7 cancer cells respectively. The obtained enhanced antitumor activity elected this delivery system for further in vivo and toxicological investigations.