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Preparation and physical chemical characterization of lipid nanoparticles as carriers of triterpenes for the treatment of visceral leishmaniasis

Grant number: 18/04080-2
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): May 12, 2018
Effective date (End): November 30, 2018
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Luiz Felipe Domingues Passero
Grantee:Jéssica Adriana de Jesus
Supervisor abroad: Domingos de Carvalho Ferreira
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Universidade do Porto (UP), Portugal  
Associated to the scholarship:16/10324-6 - Lipid nanoparticles as carriers of triterpenes for the treatment of experimental visceral leishmaniasis, BP.DR


Leishmaniasis is endemic in 98 countries and it is considered neglected by the World Health Organization. Leishmaniasis is caused by a protozoan parasite of the Leishmania genus and is transmitted by a sandfly vector. This disease presents different clinical forms, ranging from simple ulcerated skin lesion, that may disappears spontaneously, to the visceral form that affects internal organs and leads to death if left untreated. The treatment is still performed using pentavalent antimonials or amphotericin B, which causes a number of side effects, and reports of resistance to these drugs have been constantly published. These facts demonstrate that the development of new drugs or formulations directed to the chemotherapy of leishmaniasis is necessary and urgent. Recently, our group demonstrated that ursolic acid showed therapeutic activity in tegumentar and visceral leishmaniasis. In order to increase its efficiency and give continuity in this study, the project aims to prepare and characterize solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) as carriers of the triterpenes, ursolic acid (UA), maslinic acid (MA), Betulin (Be) and Lupeol (Lu) to study its efficacy in the treatment of visceral leishmaniasis. The biodistribution nanosystems (SLN and NLC) loaded with the triterpenoids will be prepared and evaluated for particle size and distribution, zeta potential, physical state and polymorphism, pH, storage stability, sterilization effects, encapsulation efficiency, drug loading capacity and the release of compounds in vitro will be analyzed. The incorporation of triterpenes into nanocarriers and physical-chemical characterization will be performed in the Laboratory of Pharmaceutical Technology of the Faculty of Pharmacy of the University of Porto, under the supervision of Prof. Dr. Domingos de Carvalho Ferreira and Prof. Dr. Paulo Jorge Cardoso da Costa, who have extensive experience in the design, production and characterization of nanosystems. The most active in vitro formulation will be analyzed in vivo. In addition, toxicity studies with the most active formulation will be conducted. All these studies will be evaluated in São Paulo. Since the studies with triterpenes conveyed with SLN and NLC are rare and the fact that these natural compounds have already been reported with leishmanicidal potential, including our in vivo studies, the realization of this study is an alternative therapeutic strategy for the treatment of experimental visceral leishmaniasis, and aims to increase the therapeutic potential of compounds of natural origin.