Thermosensitive chitosan-oxidized dextran-β-glycerophosphate sodium injectable hydrogel for enhanced solubility and prolonged release of ethinylestradiol: a novel long-acting contraceptive platform

Abstract

Ethinylestradiol (EE) is a clinically used estrogen with antifertility effects that is poorly water soluble, limiting bioavailability and preventing long-term release when administered orally. This study addresses these challenges through the development of a novel injectable thermosensitive hydrogel that both improves hydrophobic EE dispersion and enables sustained in vivo release, presenting significant potential for long-term contraception. Carboxymethyl-β-cyclodextrin (CM-β-CD) was synthesized to encapsulate EE, thereby enhancing its solubility and distribution in the hydrogel matrix. We found that hydrogels prepared by adding 0.5% (w/v) oxidized dextran (ODex) to the chitosan/sodium β-glycerophosphate (CS/ODex/β-GP) system exhibited mechanical strength favorable for cell growth compared to conventional CS/β-GP, resolved the problems of poor stability and mechanical strength of CS/β-GP hydrogels, and ensured effective retention and delivery in vivo. A 240h drug release study demonstrated the hydrogel’s ability to sustain release, highlighting its potential to prolong contraceptive efficacy. Biocompatibility testing showed cell viability in excess of 85%. FTIR and SEM characterization further confirmed the functional structure and morphology of the hydrogel. This thermosensitive injection system provides a promising platform for the long-term release of hydrophobic drugs such as EE, providing an innovative approach to extended contraceptive delivery.