Enhancing ER-Positive Breast Cancer Treatment with Drug-Loaded Microneedle Hydrogels

Abstract

Breast cancer is the leading malignancy among women globally and is marked by its heterogeneous nature, characterized by various subtypes driven by distinct genetic mutations and hormone receptor expressions. The expression of estrogen receptor (ER) increases in 70-75% of breast cancer cases, making it a central therapeutic target for treating luminal a and b breast cancer. Current treatment modalities include endocrine therapy, which utilizes anti-estrogens and aromatase inhibitors to mitigate tumor growth and proliferation. However, these therapies have limitations such as multi-drug resistance, systemic toxicity, and suboptimal bioavailability. This study focuses on developing microneedle-hydrogel systems based on chitosan and polyvinyl alcohol (PVA) for localized and sustained delivery of anticancer therapeutics. Therefore, hydrogel microneedles were synthesized followed by characterization and encapsulation with vitamin D and of drug to investigate their cytotoxic effects on breast cancer cell lines (MCF-7, HEK293 and MDA-MB-231). Findings suggest that vitamin D encapsulation within these hydrogels alters drug release kinetics, enhancing therapeutic efficacy while potentially improving patient compliance. The results from differential scanning calorimetry and Fourier-transform infrared spectroscopy indicate favorable interactions and stability of the hydrogel formulations. This approach aims to minimize systemic damage while maximizing localized therapeutic effects, highlighting the promise of microneedle hydrogels in improving breast cancer treatment outcomes.