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.
Highlights
Considering the scarcity of safe and effective approved drugs for the treatment of leishmaniasis and the activity of ursolic acid (UA) towards Leishmania species, this study aimed to develop a nanocarrier loaded with UA to enhance the effectiveness of this triterpene in experimental visceral leishmaniasis caused by L. (L.) infantum
nanostructured lipid carriers (NLCs) have been elected as an interesting drug platform to treat different intracellular infections [27], because they can access the cytoplasm of cells and deliver the content directly into the target
The steric stabilization on the surface of the nanoparticles led to negative zeta values, −26 and −29 mV for NLC and UA-NLC, respectively, suggesting that the samples remained dispersed and stable, with a reduced tendency to form aggregates due to the electrostatic repulsion [30]
Summary
Leishmaniasis is a neglected tropical disease, caused by a parasite of the genus Leishmania that is transmitted to mammalian hosts during a phlebotomine vector blood meal. Leishmaniasis has been considered a serious public health problem, given the wide geographical distribution, the number of pathogenic species to humans and other vertebrates, diversity of clinical forms, and the scarcity of drugs available for therapy [1,2]. The effectiveness of leishmaniasis treatment depends on several factors, such as drug choice, host immune response, parasite strain, treatment regimen, as well as patient compliance [3]. Miltefosine, pentamidine, paromomycin, and amphotericin B are considered second-choice drugs and complete the arsenal to treat all clinical forms of leishmaniasis [4]; these drugs have limitations due to side effects, high costs, and in some cases reduced efficacy, sometimes caused by resistant parasites [5,6]. It is essential to characterize new, efficient, affordable, and less toxic drugs or approaches to combat this neglected disease
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