Preclinical Assessment of Ursolic Acid Loaded into Nanostructured Lipid Carriers in Experimental Visceral Leishmaniasis

Author(s)

Jesus, Jessica Adriana ^[1] ; Sousa, Ilza Maria Oliveira ^[2] ; da Silva, Thays Nicolli Fragoso ^[1] ; Ferreira, Aurea Favero ^[1] ; Laurenti, Marcia Dalastra ^[1] ; Antonangelo, Leila ^{[3, 4]} ; Faria, Caroline Silverio ^[3] ; da Costa, Paulo Cardoso ^[5] ; de Carvalho Ferreira, Domingos ^[5] ; Passero, Luiz Felipe Domingues ^{[6, 7]}

Affiliation

^[1] Univ Sao Paulo, Dept Patol, Lab Patol & Doencas Infecciosas LIM50, Fac Med, Av Dr Arnaldo 455 Cerqueira Cesar, BR-01246903 Sao Paulo - Brazil

^[2] Univ Campinas UNICAMP, Fac Med Sci, Rua Tessalia Vieira Camargo 126, BR-13083871 Campinas - Brazil

^[3] Univ Sao Paulo, Hosp Clin, Dept Patol, Lab Patol Clin, Fac Med, Av Dr Eneas Carvalho Aguiar 155 Cerqueira Cesar, BR-05403000 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Hosp Clin, Lab Invest Med LIM03, Fac Med, Av Dr Arnaldo 455 Cerqueira Cesar, BR-01246903 Sao Paulo - Brazil

^[5] Univ Porto, Dept Drug Sci, Fac Pharm, Lab Pharmaceut Technol, REQUIMTE, UCIBIO, MEDTECH, Rua Jorge Viterbo Ferreira 228, P-4050313 Porto - Portugal

^[6] Sao Paulo State Univ UNESP, Inst Biosci, Praca Infante Dom Henrique S-N, BR-11330900 Sao Vicente, SP - Brazil

^[7] Sao Paulo State Univ UNESP, Inst Adv Studies Ocean, Rua Joao Francisco Bensdorp 1178, BR-11350011 Sao Vicente, SP - Brazil

• Document type: Journal article
• Source: PHARMACEUTICS; v. 13, n. 6 JUN 2021.
• Web of Science Citations: 0

Abstract

Ursolic acid, a triterpene produced by plants, displayed leishmanicidal activity in vitro and in vivo; however, the low solubility of this triterpene limits its efficacy. To increase the activity of ursolic acid (UA), this triterpene was entrapped in nanostructured lipid carriers (UA-NLC), physical-chemical parameters were estimated, the toxicity was assayed in healthy golden hamsters, and the efficacy of UA-NLC was studied in experimental visceral leishmanisis. UA-NLC exhibited a spherical shape with a smooth surface with a size of 266 nm. UA-NLC displayed low polydispersity (PDI = 0.18) and good colloidal stability (-29.26 mV). Hamsters treated with UA-NLC did not present morphological changes in visceral organs, and the levels of AST, ALT, urea and creatinine were normal. Animals infected with Leishmania (Leishmania) infantum and treated with UA-NLC showed lower parasitism than the infected controls, animals treated with UA or Amphotericin B (AmB). The therapeutic activity of UA-NLC was associated with the increase in a protective immune response, and it was associated with a high degree of spleen and liver preservation, and the normalization of hepatic and renal functions. These data indicate that the use of lipid nanoparticles as UA carriers can be an interesting strategy for the treatment of leishmaniasis. (AU)

• FAPESP's process: 18/04080-2 - Preparation and physical chemical characterization of lipid nanoparticles as carriers of triterpenes for the treatment of Visceral Leishmaniasis.
• Grantee: Jéssica Adriana de Jesus
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 16/10324-6 - Lipid nanoparticles as carriers of triterpenes for the treatment of Experimental Visceral Leishmaniasis
• Grantee: Jéssica Adriana de Jesus
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/24077-6 - Pre-clinical studies of non-invasive treatments in leishmaniasis
• Grantee: Luiz Felipe Domingues Passero
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/00468-0 - Use of drug repurposing and natural product bioprospection to characterize compounds with in vitro and in vivo leishmanicidal action
• Grantee: Luiz Felipe Domingues Passero
• Support Opportunities: Regular Research Grants