A new effective antiplasmodial compound: Nanoformulated pyrimethamine.

Autor: Pestehchian N; Department of Parasitology and Mycology, School of Medicine and Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran., Vafaei MR; Department of Parasitology and Mycology, School of Medicine and Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran., Nematolahy P; Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran., Varshosaz J; Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: varshosaz@pharm.mui.ac.ir., Yousefi HA; Department of Parasitology and Mycology, School of Medicine and Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran., Bide VZ; Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran., Kalani H; Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address: hamed.kalani@yahoo.com.
Jazyk: angličtina
Zdroj: Journal of global antimicrobial resistance [J Glob Antimicrob Resist] 2020 Mar; Vol. 20, pp. 309-315. Date of Electronic Publication: 2019 Aug 09.
DOI: 10.1016/j.jgar.2019.08.002
Abstrakt: Objectives: The aim of this study was to evaluate the efficacy of pyrimethamine-loaded poloxamer 407 nanomicelles on Plasmodium berghei strain NICD in vivo.
Methods: Pyrimethamine-loaded nanomicelles were prepared and their zeta potential, particle size and polydispersity index were measured. For antiplasmodial assessment, 54 mice were randomly divided into six groups. Four groups were infected intraperitoneally with P. berghei, whereas the two remaining groups did not receive the parasite (negative controls). Three of the P. berghei-infected groups received treatment with either pyrimethamine-loaded nanomicelles (2 mg/kg), pyrimethamine (2 mg/kg) or empty nanomicelles (2 mg/kg); the fourth group remained untreated (positive control). The parasitaemia rate, survival rate and histopathological changes in the liver, spleen and kidneys were examined and were compared with the negative and positive control groups.
Results: The mean parasitaemia rate differed significantly between the nanoformulated pyrimethamine group and each of the other groups (P<0.05). Moreover, the survival rate of mice in the nanoformulated pyrimethamine group (7/9; 78%) was significantly higher compared with each of the other groups (P<0.01). The main histopathological changes, including hepatic necrosis in the liver, lymphoid hypoplasia in the spleen, and tubular nephrosis and perivascular and interstitial lymphocytic infiltration in the kidneys, were considerably lower in the nanoformulated pyrimethamine group than in the pyrimethamine and positive control groups.
Conclusion: Pyrimethamine-loaded nanomicelles showed potent antimalarial activity and can be considered as a potential candidate for further examination of their suitability as an antimalarial drug.
(Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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