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Current Drug Delivery

Author(s): Paloma Wetler Meireles, Dandara Paiva Barroso de Souza, Marianne Grilo Rezende, Maria Paula Gonçalves Borsodi, Douglas Escrivani de Oliveira, Luiz Cláudio Rodrigues Pereira da Silva, Alessandra Mendonça Teles de Souza, Gil Mendes Viana, Carlos Rangel Rodrigues, Flavia Almada do Carmo, Valeria Pereira de Sousa, Bartira Rossi-Bergmann and Lucio Mendes Cabral*

DOI: 10.2174/1567201817666200704132348

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Nanoparticles Loaded with a New Thiourea Derivative: Development and In vitro Evaluation Against Leishmania amazonensis

Page: [694 - 702] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Leishmaniasis is a neglected tropical disease caused by protozoa of the genus Leishmania. Current treatments are restricted to a small number of drugs that display both severe side effects and a potential for parasites to develop resistance. A new N-(3,4-methylenedioxyphenyl)-N'- (2-phenethyl) thiourea compound (thiourea 1) has shown promising in vitro activity against Leishmania amazonensis with an IC50 of 54.14 μM for promastigotes and an IC50 of 70 μM for amastigotes.

Objective: To develop a formulation of thiourea 1 as an oral treatment for leishmaniasis, it was incorporated into Nanoparticles (NPs), a proven approach to provide long-acting drug delivery systems.

Methods: Poly (D,L-Lactic-co-Glycolic Acid) (PLGA) polymeric NPs containing thiourea 1 were obtained through a nanoprecipitation methodology associated with solvent evaporation. The NPs containing thiourea 1 were characterized for Encapsulation Efficiency (EE%), reaction yield (% w/w), surface charge, particle size and morphology by Transmission Electron Microscopy (TEM).

Results: NPs with thiourea 1 showed an improved in vitro leishmanicidal activity with a reduction in its cytotoxicity against macrophages (CC50>100 μg/mL) while preserving its IC50 against intracellular amastigotes (1.46 ± 0.09 μg/mL). This represents a parasite Selectivity Index (SI) of 68.49, which is a marked advancement from the reference drug pentamidine (SI = 30.14).

Conclusion: The results suggest that the incorporation into NPs potentiated the therapeutic effect of thiourea 1, most likely by improving the selective delivery of the drug to the phagocytic cells that are targeted for infection by L. amazonensis. This work reinforces the importance of nanotechnology in the acquisition of new therapeutic alternatives for oral treatments.

Keywords: Leishmaniasis, thiourea, polymeric nanoparticles, PLGA, cytotoxicity, macrophages, amastigotes, promastigotes.

Graphical Abstract

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