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

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.

Leishmaniasis and Chagas disease: Is there hope in nanotechnology to fight neglected tropical diseases?

“…The efficient delivery of ursolic acid from lipid nanoparticles stimulated expression of IFN-g and iNOS, and boosted the production of leishmania-specific IgG antibodies. Although no comparison was made with LAmpB treatment, it is clear that the encapsulation of ursolic acid offers a superior drug formulation with reduced toxicity and increased parasiticidal effect (Jesus et al, 2021).…”

Plant Bioactive Ingredients in Delivery Systems and Nanocarriers for the Treatment of Leishmaniasis: An Evidence-Based Review

“…Jesus et al observed that the compound was loaded into nanostructured lipid carriers (UANLC), and L. infantum infected golden hamsters cured with the nanocomposition, which showed no morphological alterations in their visceral tissues ( 37 ). AST, ALT, urea and creatinine were not abnormal.…”

“…In addition, the reduction of parasitic load in UA-NLC-treated hamsters was more significant than the ursolic acid-free group and the amphotericin B group. Furthermore, the beneficial activity of UANLC was linked with an increased protective immune response and a high preservation level of the spleen and liver as well as the normalization of liver and kidney functions ( 37 ).…”

Could natural terpenes be an alternative for the treatment of neglected tropical diseases?

“…Compound 15 also inhibits the growth of P. falciparum cultured in human erythrocytes (Tallorin et al, 2014) et al, 2021). This compound also demonstrated moderate activity against promastigotes of L. infantum and, L. amazonensis as well as T. cruzi amastigotes (de Jesus et al, 2021;Machado et al, 2018).…”

“…The study discovered a raised transcription of IFN-γ mRNA and expression of inducible nitric oxide synthase (iNOS) in animals treated with 6-NLC. This may partly explain the observed leishmanicidal activity (Jesus et al, 2021). In a different study, 6-NLC coated with chitosan oligosaccharide performed impressively against Leishmania in vitro and BALB/c mice with L. donovani infection.…”