Activity of Amphotericin B-Loaded Chitosan Nanoparticles against Experimental Cutaneous Leishmaniasis

Abstract

Chitosan nanoparticles have gained attention as drug delivery systems (DDS) in the medical field as they are both biodegradable and biocompatible with reported antimicrobial and anti-leishmanial activities. We investigated the application of chitosan nanoparticles as a DDS for the treatment of cutaneous leishmaniasis (CL) by preparing two types of chitosan nanoparticles: positively charged with tripolyphosphate sodium (TPP) and negatively charged with dextran sulphate. Amphotericin B (AmB) was incorporated into these nanoparticles. Both types of AmB-loaded nanoparticles demonstrated in vitro activity against Leishmania major intracellular amastigotes, with similar activity to unencapsulated AmB, but with a significant lower toxicity to KB-cells and red blood cells. In murine models of CL caused by L. major, intravenous administration of AmB-loaded chitosan-TPP nanoparticles (Size = 69 ± 8 nm, Zeta potential = 25.5 ± 1 mV, 5 mg/kg/for 10 days on alternate days) showed a significantly higher efficacy than AmBisome® (10 mg/kg/for 10 days on alternate days) in terms of reduction of lesion size and parasite load (measured by both bioluminescence and qPCR). Poor drug permeation into and through mouse skin, using Franz diffusion cells, showed that AmB-loaded chitosan nanoparticles are not appropriate candidates for topical treatment of CL.

Effect of Lipopeptide-Loaded Chitosan Nanoparticles on Candida albicans Adhesion and on the Growth of Leishmania major

“…Therefore, Cs-NPs could enhance the antileishmanial activity of LP. Similar results were observed for amphotericin B incorporated into chitosan nanoparticles which were more potent than free amphotericin B in inhibiting leishmania major promastigotes and amastigotes [45]. LP/Cs-NPs showed less toxicity than LP to human red blood cells and Raw 264.7 cells.…”

Leishmaniasis and Chagas disease: Is there hope in nanotechnology to fight neglected tropical diseases?

“…The accumulation of phagocytes from inflammation in infected tissues may have contributed to the increased nanoparticle uptake observed in infected tissues after topical administration. On the contrary, intravenous administration of AmpB-CHI increased the intralesional concentration of AmpB and decreased parasite burden in comparison to LAmpB treatment (Riezk et al, 2020).…”

Exploring Innovative Leishmaniasis Treatment: Drug Targets from Pre‐Clinical to Clinical Findings

“…Recently, Riezk et al . evaluated the in vitro antileishmanial activity of various forms of chitosan, including low, medium and high molecular weight chitosan and its derivatives, against extracellular promastigotes and intracellular amastigotes of L. major and L. mexicana [32] . In this study, the authors demonstrated for the first time a pH dependent antileishmanial activity of chitosan and its derivatives, which may justify the great variability of the antileishmanial activity of this compound in the literature.…”