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ORIGINAL RESEARCH ARTICLE

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

Anupa Sivakumar1* ,  Sunil Pazhayanur Venkateswaran2 ,  Htar Htar Aung1 ,  Jeya Seela Anandha Rao2 ,  Ammu Kutty Radhakrishnan3 ,  Shadab Md3
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1 Department of Human Biology, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
2 Department of Pathology and Pharmacology, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
3 Food as Medicine Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor, Malaysia
4 Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
CP 2025, 7(1), 96–108;
Submitted: 20 December 2024 | Revised: 11 March 2025 | Accepted: 21 March 2025 | Published: 15 April 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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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
Funding
This study was supported by a research grant from the (IMU 357/2016).
Conflict of interest
The authors declare no conflict of interest.
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