A Lipid-Based In Situ-Forming Hexagonal Phase for Prolonged Retention and Drug Release in the Breast Tissue

Author(s)

Salata, Giovanna C. ; Malago, Isabella D. ; Lopes, Luciana B.

• Document type: Journal article
• Source: AAPS PHARMSCITECH; v. 23, n. 7, p. 14-pg., 2022-09-19.

Abstract

In this study, the addition of monoolein to phosphatidylcholine (PC), tricaprylin, and propylene glycol (PG) mixtures was studied to produce fluid precursor formulations (FIPs) that could transform into hexagonal phase (resistant to aqueous dilution) in vitro and in vivo. The overall goal was to obtain FIPs that could incorporate chemopreventive drugs for subcutaneous administration in the mammary tissue to inhibit the development and/or recurrence of breast cancer. Increasing PG content reduced FIP viscosity up to similar to 2.5-fold, while increases in PC (over monoolein) increased the formation of emulsified systems. The hexagonal phase was observed at 20% of water and higher, with the minimum amount of water necessary for this formation increasing with PG content. The selected FIP formed a depot in vivo after similar to 24 h of administration; its structure was compatible with the hexagonal phase and it remained in the mammary tissue for at least 30 days, prolonging the permanence of a fluorescent probe. In vitro, the release of the synthetic retinoid fenretinide was slow, with similar to 9% of the drug released in 72 h. Consistent with this slow release, fenretinide IC50 in breast cancer cells was similar to 100-fold higher in the selected FIP compared to its solution. The FIP reduced cell migration and presented higher cytotoxicity towards tumor compared to non-tumor cells. Given the limited number of options for pharmacological prevention of breast cancer development and recurrences, this formulation could potentially find applicability to reduce the frequency of administration and improve local concentrations of chemopreventive drugs. (AU)

• 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
• 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: 19/23864-7 - Comprehensive analysis of genomic data for identification and validation of novel therapeutic targets involved in cellular cytoskeleton regulation in acute Leukemia
• Grantee: João Agostinho Machado Neto
• Support Opportunities: Regular Research Grants