Cationic Liposomal Sodium Stibogluconate (SSG), a Potent Therapeutic Tool for Treatment of Infection by SSG-Sensitive and -Resistant Leishmania donovani
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Cationic Liposomal Sodium Stibogluconate (SSG), a Potent
Therapeutic Tool for Treatment of Infection by SSG-Sensitive and -Resistant Leishmania donovani
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| Creator |
Sinha, Roma
Roychoudhury, Jayeeta Palit, Partha Ali, Nahid |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Pentavalent antimonials have been the first-line treatment for leishmaniasis for decades. However, the development of resistance to sodium stibogluconate (SSG) has limited its use, especially for treating visceral leishmaniasis (VL). The present work aims to optimize a cationic liposomal formulation of SSG for the treatment of both SSG-sensitive (AG83) and SSG-resistant (GE1F8R and CK1R) Leishmania donovani infections. Parasite killing was determined by the 3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium
bromide (MTT) assay and microscopic counting of Giemsa-stained macrophages. Macrophage uptake studies were carried out by confocal microscopic imaging. Parasite-liposome interactions were visualized through transmission electron
microscopy. Toxicity tests were performed using assay kits. Organ parasite burdens were determined by microscopic counting and limiting dilution assays. Cytokines were measured by enzyme-linked immunosorbent assays (ELISAs) and flow cytometry. Although all cationic liposomes studied demonstrated leishmanicidal activity, phosphatidylcholine (PC)-dimethyldioctadecylammonium bromide (DDAB) vesicles were most effective, followed by PC-stearylamine (SA) liposomes. Since entrapment of SSG in PC-DDAB liposomes demonstrated enhanced ultrastructural alterations in promastigotes, PC-DDAB-SSG vesicles were further investigated in vitro and in vivo. PC-DDAB-SSG could effectively alleviate SSG-sensitive and SSG-resistant L. donovani infections in the liver, spleen, and bone marrow of BALB/c mice at a dose of SSG (3 mg/kg body weight) not reported previously. The parasiticidal activity of these vesicles was attributed to better interactions with the parasite membranes, resulting in direct killing, and generation of a strong host-protective environment, necessitating a very low dose of SSG for effective cures.
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| Publisher |
American Society for Microbiology
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| Date |
2015
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2199/1/ANTIMICROBIAL_AGENTS_AND_CHEMOTHERAPY__V.__59_(_1_)_344%2D355;2015[97].pdf
Sinha, Roma and Roychoudhury, Jayeeta and Palit, Partha and Ali, Nahid (2015) Cationic Liposomal Sodium Stibogluconate (SSG), a Potent Therapeutic Tool for Treatment of Infection by SSG-Sensitive and -Resistant Leishmania donovani. Antimicrobial Agents and Chemotherapy, 59 (1). pp. 344-355. |
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| Relation |
http://dx.doi.org/10.1128/AAC.03305-14.
http://www.eprints.iicb.res.in/2199/ |
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