Mitigating breast cancer with intratumoral in situ pH-responsive abemaciclib-loaded novasome hydrogel

Abstract

Abemaciclib (AMC) is a selective CDK4/6 inhibitor widely utilised for breast cancer therapy; however, its efficacy is compromised by poor bioavailability and low aqueous solubility. This study aimed to enhance the sustained release, targeting, and efficacy of AMC via developing an intratumoral, in situ pH-responsive AMC-loaded novasome (IPANF) hydrogel. The optimal AMC-novasome was tailored using Design-Expert® software and subsequently incorporated into a chitosan/glyceryl monooleate mixture to develop IPANF. The in vivo anti-tumour efficacy and safety profile of the IPANF were evaluated using an Ehrlich ascites carcinoma model. Within 24 h, the IPANF formulation exhibited a significantly sustained drug release by 65.31% compared to the free AMC suspension. The intratumoral IPANF resulted in a profound 96.08% reduction in tumour volume, a 70.46% recovery in body weight, and a suppression of the CA 15-3 and CA 27-29 levels by 92.66% and 91.23%, respectively. Notably, a 100% survival rate was observed in the intratumoral IPANF group. Histopathological assessments firmly validated the superior therapeutic efficacy of the intratumoral IPANF hydrogel. Furthermore, the intratumoral IPANF formulation demonstrated an excellent safety profile. These findings underscore the clinical potential of the intratumoral IPANF hydrogel as a highly efficient, localised, and safe platform for advanced breast cancer treatment.