Mitigating Breast Cancer with Intratumoral In Situ pH-responsive Abemaciclib-loaded Novasome Hydrogel

Area of Science:

• Biomedical Engineering
• Drug Delivery
• Oncology

Background:

• Abemaciclib (AMC) is an FDA-approved CDK4/6 inhibitor for breast cancer.
• Clinical use of AMC is limited by poor bioavailability and solubility.
• Novel drug delivery systems are needed to improve AMC's efficacy.

Purpose of the Study:

• To develop an intratumoral, pH-responsive hydrogel loaded with AMC-novasomes (IPANF).
• To enhance sustained release, localized targeting, and therapeutic efficacy of AMC.
• To evaluate the in vivo anti-tumor efficacy and safety of the IPANF hydrogel.

Main Methods:

• AMC-novasomes were optimized using Design-Expert® software.
• Novasomes were incorporated into a chitosan/glyceryl monooleate hydrogel for pH-responsive in situ gelling.
• In vivo studies were conducted using an Ehrlich ascites carcinoma tumor model.

Main Results:

• The optimized IPANF formulation showed sustained drug release, reducing cumulative release by 65.31% within 24 hours.
• Intratumoral IPANF administration led to a 96.08% reduction in tumor volume and suppressed biomarkers CA 15-3 and CA 27-29.
• A 100% survival rate was observed in the IPANF-treated group with increased intratumoral drug exposure and an excellent safety profile.

Conclusions:

• The intratumoral IPANF hydrogel demonstrates significant potential for localized and sustained delivery of AMC.
• This formulation offers enhanced anti-tumor efficacy and improved safety for advanced breast cancer treatment.
• IPANF represents a promising platform for localized cancer therapy.