Chitosan Based thermosensitive In Situ Hydrogel for localized Delivery of Exemestane loaded micelles: A Novel Strategy for Enhanced Breast Cancer Therapy

Abstract Targeted delivery of therapeutic agents to specific sites holds promise for enhancing drug concentration at the intended location. This study aims to develop novel micelles formulated using a Chrysin-Pluronic L121 conjugated polymer for the encapsulation of exemestane. Additionally, the micellar formulation is incorporated into thermosensitive injectable hydrogels to facilitate its localized administration and improve the therapeutic efficacy in the treatment of breast cancer. The prepared thermosensitive hydrogels demonstrated favorable gelation properties in terms of both time and temperature. In vitro release studies revealed a gradual and sustained release of EXE and CHS over a period of 72 h. Evaluation through in vitro cytotoxicity assays, confocal microscopy, and western blot analysis revealed a superior synergistic effect of EXE with CHS Additionally, the in situ thermosensitive hydrogel facilitated enhanced accumulation of EXE and CHS at the injection site. In vivo studies conducted on BALB/c mice bearing tumors demonstrated tumor inhibition, highlighting the potential of this localized delivery system. Overall, the incorporation of in situ hydrogel presents a promising strategy for effectively treating hormone-related breast cancer, offering improved therapeutic efficacy and safety.