Affiliation:
1. Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
2. Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
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 Method: NPs of 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.
Publisher
Bentham Science Publishers Ltd.
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献