Potential Oral Anticancer Therapeutic Agents of Hexahydrocurcumin-Encapsulated Chitosan Nanoparticles against MDA-MB-231 Breast Cancer Cells

Author:

Sorasitthiyanukarn Feuangthit N.12ORCID,Muangnoi Chawanphat3,Gomez Clinton B.4ORCID,Suksamrarn Apichart5,Rojsitthisak Pranee12ORCID,Rojsitthisak Pornchai26ORCID

Affiliation:

1. Metallurgy and Materials Science Research Institute, Chulalongkorn University, Bangkok 10330, Thailand

2. Center of Excellent in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand

3. Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand

4. Department of Industrial Pharmacy, College of Pharmacy, University of the Philippines Manila, Manila 1000, Metro Manila, Philippines

5. Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand

6. Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand

Abstract

Hexahydrocurcumin-encapsulated chitosan nanoparticles (HHC-CS-NPs) were formulated by oil-in-water emulsification and ionotropic gelation and optimized using the Box–Behnken design. The particle size, zeta potential, and encapsulation efficiency of the optimized HHC-CS-NPs were 256 ± 14 nm, 27.3 ± 0.7 mV, and 90.6 ± 1.7%, respectively. The TEM analysis showed a spherical shape and a dense structure with a narrow size distribution. The FT-IR analysis indicated no chemical interaction between the excipients and the drugs in the nanoparticles, but the existence of the drugs was molecularly dispersed in the nanoparticle matrices. The drug release profile showed a preliminary burst release followed by a sustained release under simulated gastrointestinal (GI) and physiological conditions. A stability study suggested that the HHC-CS-NPs were stable under UV light, simulated GI, and body fluids. The in vitro bioaccessibility and bioavailability of the HHC-CS-NPs were 2.2 and 6.1 times higher than those of the HHC solution, respectively. The in vitro evaluation of the antioxidant, anti-inflammatory, and cytotoxic effects of the optimized HHC-CS-NPs demonstrated that the CS-NPs significantly improved the biological activities of HHC in radical scavenging, hemolysis protection activity, anti-protein denaturation, and cytotoxicity against MDA-MB-231 breast cancer cells. Western blot analysis showed that the apoptotic protein expression of Bax, cytochrome C, caspase-3, and caspase-9, were significantly up-regulated, whereas the anti-apoptotic protein Bcl-2 expression was down-regulated in the HHC-CS-NP-treated cells. Our findings suggest that the optimized HHC-CS-NPs can be further developed as an efficient oral treatment for breast cancer.

Funder

the Ratchadaphiseksomphot Endowment Fund, Chulalongkorn University

the Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University

Publisher

MDPI AG

Subject

Pharmaceutical Science

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