Mitigating Breast Cancer with Intratumoral In Situ pH-responsive Abemaciclib-loaded Novasome Hydrogel.
TL;DR
Findings underscore the clinical potential of the intratumoral IPANF hydrogel as a highly efficient, localized, and safe platform for advanced breast cancer treatment and validate the superior therapeutic efficacy of the hydrogel.
Abstract
Abemaciclib (AMC) is an FDA-approved selective CDK4/6 inhibitor widely utilized for breast cancer therapy; however, its clinical efficacy is compromised by poor oral bioavailability and low aqueous solubility. This study aimed to enhance the sustained release, localized targeting, and therapeutic efficacy of AMC through the development of 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 impart pH-responsive in situ gelling properties. The in vivo anti-tumor efficacy and safety profile of the formulated IPANF were evaluated using an Ehrlich ascites carcinoma tumor model. Within 24 hours, the optimized IPANF formulation exhibited a significantly sustained drug release profile, reducing cumulative release by 65.31% compared to the free AMC suspension. Localized intratumoral administration of IPANF resulted in a profound 96.08% reduction in tumor volume, a 70.46% recovery in body weight, and a suppression of the breast cancer biomarkers CA 15-3 and CA 27-29 by 92.66% and 91.23%, respectively. Notably, a 100% survival rate was observed in the IPANF-treated group, accompanied by a marked increase in intratumoral drug exposure. Histopathological assessments firmly validated the superior therapeutic efficacy of the hydrogel. Furthermore, the IPANF formulation demonstrated an excellent safety profile. These findings underscore the clinical potential of the intratumoral IPANF hydrogel as a highly efficient, localized, and safe platform for advanced breast cancer treatment.