title: Development and Evaluation of a Nanoemulsion Containing Ursolic Acid: a Promising Trypanocidal Agent : Nanoemulsion with Ursolic Acid Against T. cruzi.
abstract: Over a hundred years after the discovery of Chagas disease, this ailment continues to affect thousands of people. For more than 40 years, only two drugs have been available to treat it. Ursolic acid is a naturally occurring terpene that has shown a good trypanocidal action. However, the hydrophobicity of this compound presents a challenge for the development of proper delivery systems. Nanostructured systems are a prominent in delivering lipophilic drugs. Thus, a nanoemulsion containing ursolic acid was developed and had its trypanocidal activity and cytotoxicity evaluated. Pseudo-ternary phase diagrams and hydrophilic-lipophilic balance (HLB) system were used in the development. The system was stable throughout 90 days of testing, as evidenced by turbidimetry analysis and measurements of the droplet size (57.3 nm) and polydispersity index (0.24). Fourier transform infrared spectroscopy and mass spectrometry evidenced drug's integrity in the formulation. An in vitro dissolution profile showed 75% of ursolic acid release after 5 min from the nanoemulsion into the alkaline dissolution medium, while only 20% could be released from a physical mixture after 2 h. Trypanocidal activity and cytotoxicity were evaluated on the CL Brener strain and LLC-MK2 (monkey kidney) fibroblast by chlorophenol red-β-D-galactoside (CPRG) method. Biological studies showed that the developed formulation was nontoxic and effective against replicant forms of the parasite. A stable and efficient nanoemulsion could be developed to improve the delivery of a promising drug to treat a threatening illness such as Chagas disease.
authors.affiliation: Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Avenida do Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil. erikacvargas@uol.com.br.|Department of Pharmaceutical Sciences, College of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. Zeferino Vaz, s/n, Bairro Monte Alegre, 14040-903, Ribeirão Preto, SP, Brazil. erikacvargas@uol.com.br.
authors.forename: Erika Cristina
authors.initials: EC
authors.lastname: Vargas de Oliveira
authors.affiliation: Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Avenida do Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Zumira Aparecida
authors.initials: ZA
authors.lastname: Carneiro
authors.affiliation: Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Avenida do Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Sérgio
authors.initials: S
authors.lastname: de Albuquerque
authors.affiliation: Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Avenida do Café s/n, 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Juliana Maldonado
authors.initials: JM
authors.lastname: Marchetti
mesh_terms: D014355:Chagas Disease / Q000188:drug therapy; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D049329:Nanostructures / Q000737:chemistry; D012995:Solubility; D014315:Triterpenes / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000097245:Ursolic Acid
chemical_list: D004655:Emulsions; D014315:Triterpenes; D014344:Trypanocidal Agents; D000097245:Ursolic Acid
keywords: Chagas disease; nanoemulsions; nanotechnology; ursolic acid