Development of topical curcumin nanoemulsion and comparing its anticancer effects with oral curcumin in a syngeneic mouse model of breast cancer

Abstract

Current breast cancer (BC) treatments often cause side effects, and prolonged use can lead to drug resistance. Hence, there is a demand for alternative treatment options for BC, particularly those utilizing natural compounds with better selectivity and lower toxicity. Curcumin (Cur) is a natural compound with anticancer effects but suffers from low bioavailability, accentuating the need for improved delivery systems. Transdermal drug delivery offers better patient compliance and site-specific delivery for improved treatment. In this study, a formulation of Cur-nanoemulsion (Cur-NE) was developed and characterized. The anticancer potential of the Cur-NE was evaluated using a syngeneic BC mouse model. Cancer was induced by injecting 4T1 murine mammary cancer cells into the breast pad of female Bagg Albino/c (BALB/c) mice. Treatments were started when the tumor was palpable on day 11. Tumor growth was monitored regularly. Upon sacrifice, the tumor, lungs, and liver were harvested from all animals for histopathological, immunohistochemistry (IHC), and gene expression analysis. Histological assessment revealed a higher percentage of necrosis area (25 - 70%) in tumor tissues from mice fed with Cur compared to animals fed with vehicle (10 - 50%) and those that received topical application of the Cur-NE (10 - 40%). The IHC analysis of the BC for biomarkers such as CD9, tissue inhibitor of metalloproteinases-1, and matrix metalloproteinase-13 showed higher immunoreactivity scores in the animals that received topical application of Cur-NE compared to the vehicle-fed group. The expression of four candidate genes (CDH1, TWIST1, apoptosis inhibitor-5, and CD274) was downregulated (p<0.05) in the Cur-NE group compared to the group fed with Cur. These results suggest that topical application of Cur-NE had higher anticancer effects than oral administration of Cur, making it a promising approach for the treatment of BC.

Keywords

Curcumin / Nanoemulsion / Transdermal delivery / Breast cancer / Gene expression / Immunohistochemistry