Potential of Pluronics® P-123 and F-127 as nanocarriers of anti-Leishmania chemotherapy

Acta Trop. 2019 Apr:192:11-21. doi: 10.1016/j.actatropica.2019.01.008. Epub 2019 Jan 16.

Abstract

Leishmaniasis is a neglected disease and drugs approved for its treatment often lead to abandonment, failure of therapy and even death. Photodynamic therapy (PDT) has been shown to be a promising, non-invasive and selective for a target region without requiring high-cost technology. Usually, it is employed a photosensitizing agent (PS) incorporated into nanoparticles (NP). Pluronics® P-123 and F-127 micelles are very interesting aqueous NP promoting efficient and selective delivery and less adverse effects. This study aimed to detect the activity of Pluronics® P-123 and F-127 themselves since there is a scarcity of data on these NP activities without drugs incorporation. This study evaluated, in vitro, the activity of Pluronics® against promastigotes and amastigotes of Leishmania amazonensis and also their cytotoxicities. Additionally, the determination of the mitochondria membrane potential in promastigotes, internalization of these Pluronics® in the parasite membrane and macrophages and its stability in the culture medium was evaluated. Results showed that Pluronics® did not cause significant damage to human red cells and promastigotes. The P-123 and F-127 inhibited the survival rate of L. amazonensis amastigotes, and also presented loss of mitochondrial membrane potential on promastigotes. The Pluronics® showed low cytotoxic activity on J774A.1 macrophages, while only P-123 showed moderate cytotoxicity for BALB/c macrophages. The stability of P-123 and F-127 in culture medium was maintained for ten days. In conclusion, the NP studied can be used for incorporating potent leishmanicidal chemotherapy, due to their selectivity towards macrophages, being a promising system for the treatment of cutaneous leishmaniasis.

Keywords: Cutaneous leishmaniasis; Drug carriers; Leishmania amazonensis; Polymeric micelle; Toxicity.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / methods*
  • Erythrocytes / drug effects
  • Female
  • Leishmania / drug effects*
  • Macrophages / drug effects
  • Membrane Potential, Mitochondrial
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Photochemotherapy / methods*
  • Poloxamer / pharmacology*

Substances

  • Poloxamer