Optimization of nanoemulsified systems containing lamellar phases for co-delivery of celecoxib and endoxifen to the skin aiming for breast cancer chemoprevention and treatment

Author(s)

Mojeiko, Gabriela ; Apolinario, Alexsandra Conceica ; Salata, Giovanna Cassone ; Chorilli, Marlus ; Lopes, Luciana B.

• Document type: Journal article
• Source: COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS; v. 646, p. 14-pg., 2022-08-05.

Abstract

We proposed an innovative nanoemulsified system containing lamellar phases (NLP) produced by a low-energy method to enable the local-transdermal co-delivery of celecoxib and endoxifen as a potential strategy for breast cancer local chemoprevention. The NLPs were composed of surfactant:oil phase at 1:1 (w/w) and 80% water. Oleic or caprylic acid was added (2% or 5% w/w) as penetration enhancer. NLP droplet size was influenced by the type and concentration of the penetration enhancer, ranging from 290 to 450 nm with negative zeta potential. They presented pseudoplastic behavior, and after drug addition, elastic and bioadhesive properties were displayed. Compared to water (control), all formulations increased transepidermal water loss by 8.5-12.9 times, with the NLP containing 5% oleic acid promoting a more pronounced effect. No signs of vascular toxicity were observed in the HET-CAM model, suggesting safety. All NLPs increased the penetration of celecoxib and endoxifen in the skin, but the formulation containing 5% oleic acid was more effective, promoting 3-22-fold increases in cutaneous delivery and 11-20-fold increases in transdermal drug delivery. Combination of celecoxib and endoxifen in this NE reduced the viability of cancer cells in a synergistic manner compared to the use of isolated drugs. These results suggest the potential applicability of the NE for topical delivery and breast cancer chemoprevention. (AU)

• FAPESP's process: 19/26048-6 - Development and application of multifunctional nanocarriers for intraductal delivery of chemotherapy aiming at Breast Cancer treatment
• Grantee: Giovanna Cassone Salata
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/14375-0 - Nanotechnology-based topical delivery systems for breast cancer chemoprevention
• Grantee: Alexsandra Conceição Apolinário
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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
• FAPESP's process: 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors
• Grantee: Luciana Biagini Lopes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants