Encapsulation of the HSP-90 Chaperone Inhibitor 17-AAG in Stable Liposome Allow Increasing the Therapeutic Index as Assessed, in vitro , on Leishmania (L) amazonensis Amastigotes-Hosted in Mouse CBA Macrophages

Frontiers in Cellular and Infection Microbiology
Antonio Luis de Oliveira Almeida PetersenPatricia S T Veras

Abstract

The current long-term treatment for leishmaniasis causes severe side effects and resistance in some cases. An evaluation of the anti-leishmanial potential of an HSP90-inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), demonstrated its potent effect against Leishmania spp. in vitro and in vivo. We have previously shown that 17-AAG can kill L. (L) amazonensis promastigotes with an IC50 of 65 nM and intracellular amastigote at concentrations as low as 125 nM. As this compound presents low solubility and high toxicity in human clinical trials, we prepared an inclusion complex containing hydroxypropyl-β-cyclodextrin and 17-AAG (17-AAG:HPβCD) to improve its solubility. This complex was characterized by scanning electron microscopy, and X-ray diffraction. Liposomes-containing 17-AAG:HPβCD was prepared and evaluated for encapsulation efficiency (EE%), particle size, polydispersity index (PDI), pH, and zeta potential, before and after accelerated and long-term stability testing. An evaluation of leishmanicidal activity against promastigotes and intracellular amastigotes of L. (L) amazonensis was also performed. The characterization techniques utilized confirmed the formation of the inclusion complex, HPβCD:17-AAG, with a result...Continue Reading

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Citations

Jan 31, 2019·Chemical Biology & Drug Design·Sona TalaeiNosratollah Zarghami
Nov 30, 2019·International Journal of Molecular Sciences·Tawanda Zininga, Addmore Shonhai
Nov 4, 2020·Infection and Immunity·Pragya Prasanna, Arun Upadhyay
Feb 5, 2021·Parasitology·Sajad RashidiPaul Nguewa
Jun 1, 2021·Frontiers in Chemistry·Kercia P CruzPatrícia S T Veras

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Methods Mentioned

BETA
X-ray
scanning electron microscopy
infrared spectroscopy
dynamic light scattering
transmission electron microscopy
FCS
lavage
confocal microscopy
differential scanning calorimetry

Software Mentioned

GraphPad Prism

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