Topical delivery of endoxifene and celecoxib using nanocarriers as a new alternative for breast cancer prevention.

Author(s)

Gabriela Mojeiko

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2021-06-24

Examining board members

Luciana Biagini Lopes; André Rolim Baby; Gislaine Ribeiro Pereira; Ana Flavia Marçal Pessoa

• Advisor: Luciana Biagini Lopes

Abstract

Despite the high incidence of breast cancer, there are few strategies for its prevention and these have limited adherence mainly due to its serious adverse effects, highlighting the need for new drugs and forms of prevention. In this study, we developed and evaluated topical nanocarriers for self-administration of a combination of drugs (celecoxib and endoxifen) directly on the breast skin, to optimize the deep penetration in the skin and the location of the drugs in the breast tissue. Two nanocarriers were compared: nanoemulsions stabilized by lamellar liquid-crystalline phase and etosomes. Lamellar phase-stabilized nanoemulsions were composed of surfactant: 5: 5 (w / w) oil phase, with 80% water and 2 or 5% (w / w) oleic or caprylic acid as penetration enhancers. Binary etosomal systems were developed with phosphatidylcholine, two alcohols (ethanol and propylene glycol) and water The droplet size of the nanoemulsions was not influenced by the type or concentration of the penetration enhancer, ranging from 470.5 to 585.5 nm. They were characterized as non-Newtonian systems of the pseudoplastic type, and the formulation containing the drugs displayed elastic and bioadhesive properties. Compared to water (control), all formulations increased TEWL by 8.5-12.9 times. The nanoemulsion containing 5% oleic acid promoted a more pronounced increase compared to the control (12,9 fold). Despite this increase, they were considered non-irritant in the HET-CAM model. All nanoemulsions increased the penetration of drugs into viable layers of the skin, but the formulation containing 5% oleic acid was more effective, increasing ipenetrating into viable layers by 3,2-22,4-fold, and the transdermal transport of endoxifene (61,5 -fold) and celecoxib (11,56-fold). The selected ethosomal system was composed of 4% phosphatidylcholine, 0.7% celecoxib and 0.5% endoxifene and presented size of 461.1 nm. Its was included in an sodium alginate gel. This system did not influence the transepidermal water loss, however, compared to the control, there was an increase in the cutaneous penetration in the viable layers (2 - 3 times) and the receptor phase (3.2 - 31 times) for the drugs celecoxib and endoxifene respectively. The nanoemulsion containing 5% oleic acid reduced the viability of cancer cells compared to the use of isolated drugs. These results suggest the potential applicability of the nanoemulsion for topical breast cancer chemoprevention. (AU)

• FAPESP's process: 19/00196-9 - Topical delivery of endoxifene and celecoxib using nanogels as a new alternative for the chemoprevention of breast tumors
• Grantee: Gabriela Mojeiko
• Support Opportunities: Scholarships in Brazil - Master