Incorporation of Ursolic Acid in Liquid Crystalline Systems Improves the Antifungal Activity AgainstCandidaSp

Author(s)

Marena, Gabriel Davi ; Fonseca-Santos, Bruno ; Matheus Aparecido dos Santos, Ramos ; dos Santos, Karen Cristina ; Bauab, Tais Maria ; Chorilli, Marlus

• Document type: Journal article
• Source: JOURNAL OF PHARMACEUTICAL INNOVATION; v. 16, n. 4, p. 11-pg., 2020-07-10.

Abstract

Purpose Infectious diseases caused byCandidasp. have high drug resistance due to the uncontrolled use of antibiotics. Among the natural products, ursolic acid (UA), a triterpene, has been increasing interest due to its antimicrobial effects. However, the physicochemical properties of UA, such as its low aqueous solubility, lead to failure of therapeutic application. Because of this, drug release systems, such as liquid crystals (LCs), can improve solubilization and increase the therapeutic efficacy of many drugs. Methods In this work, we evaluated the antifungal potential of UA and loaded into LC precursor system againstCandidasp. The system was composed of oleic acid (30%), polysorbate 80 (60%), and purified water (10%). Polarized light microscopy, rheological assays, and simulated vaginal fluid (SVF) simulations were performed. Cytotoxicity assay was evaluated against L-929 cells (murine fibroblast), and antifungal evaluation was performed by microplate microdilution method againstCandida albicans,Candida glabrata,Candida krusei,Candida parapsilosis, andCandida tropicalis. Results The system showed acceptable parameters for UA incorporation, such as adhesiveness, texture, and flow behaviors, compatible to vaginal administration. Free UA showed no antifungal activity; however, after incorporation into LCs, it was observed againstC. albicans,C. glabrata,C. tropicalis, andC. parapsilosis(MIC values around 500 mu g/mL and 3.9 mu g/cell viability assays showed moderate cytotoxicity [halo diameter 1.00 +/- 0.156]). Conclusion In conclusion, the results corroborate in the materials field as a possible alternative in the treatment of infectious diseases byCandidaspecies and the systems showed potential promising for enhancing AU antifungal performance with the application on vulvovaginitis. (AU)

• FAPESP's process: 18/23442-2 - Evaluation of the potential of liposomes for co-encapsulation of amphotericin B and micafungin in the treatment of systemic infection caused by Candida auris
• Grantee: Matheus Aparecido dos Santos Ramos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral