Poloxamer 407 (Pluronic® F127)-based polymeric micelles for amphotericin B : in vitro biological activity, toxicity and in vivo therapeutic efficacy against murine tegumentary leishmaniasis.
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2016
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In the present study, a Poloxamer 407-based amphotericin B (AmpB)-containing polymeric micelles
system (AmpB/M) was employed in the treatment of Leishmania amazonensis-infected BALB/c mice.
Initially, the in vitro antileishmanial activity (IC50 value) of AmpB/M and B-AmpB/M (empty micelles)
against stationary promastigotes and amastigotes-like forms of the parasites was determined, and results
were of 1.83 ± 0.4 and 22.1 ± 0.7 mM, respectively, for the promastigotes, and of 2.27 ± 0.5 and
33.98 ± 2.6 mM, respectively, for the amastigotes-like. The cytotoxic concentration (CC50) values of these
products were also evaluated, and we found the results of 119.5 ± 9.6 and 134.7 ± 10.3 mM, respectively.
With these values, the selectivity index (SI) was calculated and results were of 65.3 and 5.4, respectively, for the promastigotes, and of 59.3 and 3.96, respectively, for the amastigotes-like of the parasites. Free
AmpB showed IC50 values of 1.2 ± 0.3 and 2.5 ± 0.5 mM for the promastigotes and amastigotes-like,
respectively, whereas the CC50 value was of 9.5 ± 0.4 mM. The SI values of this drug were of 7.9 and
3.8, respectively, for the promastigote and amastigote-like stages of the parasites. After, animals were
infected and received saline or were treated subcutaneously with free AmpB, AmpB/M or B-AmpB/M. In
the results, free AmpB-treated and infected mice showed reductions in their body weight, which were
associated with hepatic and renal damage; however, no organic alteration was observed in the AmpB/Mtreated
animals. In addition, these animals showed significant reductions in their lesion average size and
in the parasite burden in all evaluated infected tissue and organs, when compared to the other groups; as
well as significantly higher levels of antileishmanial IFN-g, IL-12, GM-CSF and nitrite, which were
associated with low production of IL-4, IL-10 and IgG1 isotype antibodies. In conclusion, this AmpB/M
system could be considered as an alternative for future studies in the treatment of tegumentary
leishmaniasis.
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MENDONÇA, D. V. C. et al. Poloxamer 407 (Pluronic® F127)-based polymeric micelles for amphotericin B : in vitro biological activity, toxicity and in vivo therapeutic efficacy against murine tegumentary leishmaniasis. Experimental Parasitology, v. 169, p. 34-42, 2016. Disponível em: <http://www.sciencedirect.com/science/article/pii/S0014489416301412>. Acesso em: 29 ago. 2017.