Evaluation of nanoemulsions for local topical-transdermal administration of fenretinide for pharmacological prevention and adjuvant therapy for breast cancer.

Author(s)

Jéssica Ribeiro Nunes

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2024-02-01

Examining board members

Luciana Biagini Lopes; Maria Teresa Junqueira Garcia; Analí Del Milagro Bernabé Garnique; Fabiana Testa Moura de Carvalho Vicentini

• Advisor: Luciana Biagini Lopes

Abstract

To contribute to the development of new local pharmacological strategies for prevention and adjuvant treatment of breast cancer, nanoemulsions (NE) were studied for topical-transdermal delivery of the retinoid fenretinide to the breast skin. The monoterpene limonene was incorporated with the dual role of enhancing penetration and cytotoxicity. The influence of the type of liquid lipid used as oil phase and concentration of limonene on the physicochemical properties of the nanoemulsion were studied. All nanoemulsions displayed a diameter bellow 200 nm, low polidispersity (PDI0.2) and anionic zeta potential (approximately -10 mV). Higher terpene concentrations showed a tendency to reduce diameter. The nanoemulsions did not show signs of local irritation in the HET-CAM model, regardless of limonene concentration. However, only the systems containing isopropyl myristate with limonene at 1 and 2.5% remained stable for 6 months, and enabled fenretinide incorporation at 1%. The skin penetration of fenretinide, assessed in Franz diffusion cells and porcine ear skin, increased with time and limonene concentration, with 2.5% of limonene providing higher quantities of the drug in viable layers of the skin (5.8-fold compared to the control solution at 12 h). Additionally, the combination of limonene and fenretinide resulted in an increased drug cytotoxicity compared with the nanoemulsion without limonene (a decrease in 2 to 4-fold IC50 values). However, few differences are shown compared to the drug solution. The NE with limonene and fenretinide was also capable of significantly reduce breast cancer cells migration (in 2-fold compare with the NE with limonene without drug), confirming its potential applicability for the proposed aims. (AU)

• FAPESP's process: 21/06755-0 - Evaluation of nanoemulsions for local-transdermal administration of fenretinide for breast cancer chemoprevention
• Grantee: Jessica Ribeiro Nunes
• Support Opportunities: Scholarships in Brazil - Master