Therapy with Sodium Stibogluconate in Stearylamine- Bearing Liposomes Confers Cure against SSG-Resistant Leishmania Donovani in BALB/c Mice
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Therapy with Sodium Stibogluconate in Stearylamine-
Bearing Liposomes Confers Cure against SSG-Resistant
Leishmania Donovani in BALB/c Mice
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| Creator |
Roychoudhury, Jayeeta
Sinha, Roma Ali, Nahid |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Background: Resistance of Leishmania donovani to pentavalent antimonials, the first-line treatment of visceral leishmaniasis
(VL), has become a critical issue worldwide. Second-line and new drugs are also not devoid of limitations. Suitable drugdelivery
systems can improve the mode of administration and action of the existing antimonials, thus increasing their
clinical life.
Methodology/Principal Findings: We investigated the efficacy of sodium stibogluconate (SSG) in phosphatidylcholine (PC)–
stearylamine-bearing liposomes (PC-SA-SSG), PC-cholesterol liposomes (PC-Chol-SSG) and free amphotericin B (AmB)
against SSG-resistant L. donovani strains in 8-wk infected BALB/c mice. Animals were sacrificed and parasites in liver, spleen
and bone marrow were estimated 4-wk post-treatment by microscopic examination of stamp smears and limiting dilution
assay. A set of PC-SA-SSG and AmB treated mice were further studied for protection against reinfection. Serum antibodies
and cytokine profiles of ex-vivo cultured splenocytes were determined by ELISA. Uptake of free and liposomal SSG in
intracellular amastigotes was determined by atomic absorption spectroscopy. Rhodamine 123 and 5-carboxyfluorescein,
known substrates of Pgp and MRP transporter proteins, respectively, were used in free and liposomal forms for efflux
studies to estimate intracellular drug retention. Unlike free and PC-Chol-SSG, PC-SA-SSG was effective in curing mice
infected with two differentially originated SSG-unresponsive parasite strains at significantly higher levels than AmB.
Successful therapy correlated with complete suppression of disease-promoting IL-10 and TGF-b, upregulation of Th1
cytokines and expression of macrophage microbicidal NO. Cure due to elevated accumulation of SSG in intracellular
parasites, irrespective of SSG-resistance, occurs as a result of increased drug retention and improved therapy when
administered as PC-SA-SSG versus free SSG.
Conclusions/Significance: The design of this single-dose combination therapy with PC-SA-SSG for VL, having reduced
toxicity and long-term efficacy, irrespective of SSG-sensitivity may prove promising, not only to overcome SSG-resistance in
Leishmania, but also for drugs with similar resistance-related problems in other diseases.
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| Date |
2011
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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/121/1/PLOS_ONE%2C6(3)%2C2011[81].pdf
Roychoudhury, Jayeeta and Sinha, Roma and Ali, Nahid (2011) Therapy with Sodium Stibogluconate in Stearylamine- Bearing Liposomes Confers Cure against SSG-Resistant Leishmania Donovani in BALB/c Mice. PLOS ONE, 6 (3). |
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| Relation |
http://dx.doi.org/10.1371/journal.pone.0017376
http://www.eprints.iicb.res.in/121/ |
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