1. Activity of Amphotericin B-Loaded Chitosan Nanoparticles against Experimental Cutaneous Leishmaniasis
- Author
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Sudaxshina Murdan, Alaa Riezk, Simon L. Croft, Vanessa Yardley, and Katrien Van Bocxlaer
- Subjects
Administration, Topical ,Pharmaceutical Science ,02 engineering and technology ,Pharmacology ,Analytical Chemistry ,Amphotericin B ,Drug Discovery ,Leishmania major ,Skin ,0303 health sciences ,Mice, Inbred BALB C ,biology ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,Antimicrobial ,in vivo ,Chemistry (miscellaneous) ,Drug delivery ,Toxicity ,Molecular Medicine ,0210 nano-technology ,medicine.drug ,chitosan nanoparticles ,Sodium ,Antiprotozoal Agents ,chemistry.chemical_element ,Leishmaniasis, Cutaneous ,Article ,Permeability ,lcsh:QD241-441 ,cutaneous leishmaniasis ,03 medical and health sciences ,lcsh:Organic chemistry ,Cutaneous leishmaniasis ,In vivo ,medicine ,Animals ,Parasites ,Physical and Theoretical Chemistry ,Chitosan ,030306 microbiology ,Organic Chemistry ,technology, industry, and agriculture ,biology.organism_classification ,medicine.disease ,Disease Models, Animal ,Drug Liberation ,chemistry ,Nanoparticles - 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.
- Published
- 2020