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Harmine: Evaluation of its Antileishmanial Properties in Various Vesicular Delivery Systems

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Title Harmine: Evaluation of its Antileishmanial Properties in Various Vesicular Delivery Systems
 
Creator Lala, Sanchita
Pramanick, Swapan
Mukhopadhyay, Sibabrata
Bandyopadhyay, Santu
Basu, Mukul Kumar
 
Subject Chemistry
Drug Development/Diagnostics & Biotechnology
Infectious Diseases and Immunology
 
Description Harmine, a beta-carboline amine alkaloid isolated from Peganum harmala, was tested for its
antileishmanial properties both in vitro and in vivo. In vitro antileishmanial activity of harmine was
encouraging and prompted us to confirm the activity in vivo in hamster models. Harmine was tested
both in free form and in different vesicular forms viz. liposomes, niosomes and nanoparticles. The
different vesicles were prepared by the published protocols. The percent intercalation of harmine in
liposomes, niosomes and nanoparticles was found to be 65, 60 and 20, respectively, when determined at
325 nm (2M ¼ 2.33 £ 104M21 cm21). At an equivalent dose of 1.5 mg/kg body weight, injected
subcutaneously (SC) for a total of six doses in 15 days, harmine was found to reduce spleen parasite
load by approximately 40, 60, 70 and 80%, respectively in free, liposomal, niosomal and nanoparticular
forms. An inverse relationship could be established between the efficacy in the lowering of spleen
parasite load and the size of the vesicles. Specific biochemical tests related to normal liver and kidney
functions revealed that the toxicity of the drug was reduced in the vesicular forms in the same order as
their efficacy and the same was confirmed by the histopathological studies of splenic sections. Cell
cycle analysis studies using flow cytometry suggested that although harmine interferes in the cell
division stage, it does not induce apoptosis in Leishmania donovani promastigotes. The results using
Confocal Microscopy supported that the cell death could be attributed to necrosis due to non-specific
membrane damage. Even then, because of its appreciable efficacy in destroying intracellular parasites
as well as non-hepatotoxic and non-nephrotoxic nature, harmine, in the vesicular forms, may be
considered for clinical application in humans
 
Publisher Taylor & Francis
 
Date 2004
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1624/1/J._Drug_Targeting%2C_2004.pdf
Lala, Sanchita and Pramanick, Swapan and Mukhopadhyay, Sibabrata and Bandyopadhyay, Santu and Basu, Mukul Kumar (2004) Harmine: Evaluation of its Antileishmanial Properties in Various Vesicular Delivery Systems. Journal of Drug Targeting, 12 (3). pp. 165-175. ISSN 1061-186X
 
Relation http://dx.doi.org/10.1080/10611860410001712696
http://www.eprints.iicb.res.in/1624/