Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation
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| Creator |
Banerjee, Antara
De, Manjarika Ali, Nahid |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Visceral leishmaniasis (VL) caused by the parasite Leishmania donovani is a potentially fatal disease.
Available limited drugs are toxic, require prolonged treatment duration, and are costly. A low-cost parenteral
formulation of paromomycin sulfate (PM) has recently been approved for the treatment of VL. Monotherapy
with PM runs the risk of development of resistance. Hence, efforts are needed to develop a combination therapy
of PM with other drugs to shorten the duration of treatment and prolong the effective life of the drug. PM was
formulated with leishmanicidal stearylamine (SA)-bearing phosphatidylcholine (PC) liposomes for low-dose
therapy. In vitro and in vivo antileishmanial effects of the combination drug were determined. The immunomodulatory
role of PC-SA–PM was determined using enzyme-linked immunosorbent assay (ELISA) and flow
cytometry. Excluding the spleen, for which the therapeutic effect was additive, a remarkable synergistic activity
toward cure and prophylaxis with a single-shot low-dose treatment with PC-SA-associated PM was achieved
with BALB/c mice. PC-SA–PM showed an immunomodulatory effect on CD4� and CD8� T cells for gamma
interferon (IFN-�) production and downregulated disease-associated interleukin-10 (IL-10) and transforming
growth factor � (TGF-�) to almost negligible levels. Such combination chemotherapy may provide a promising
alternative for the cure of leishmaniasis, with a plausible conversion of the host immune response from a
disease-promoting pattern to a Th1-biased response indicative of long-term resistance.
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| Publisher |
American Society for Microbiology
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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/92/1/ANTIMICROBIAL_AGENTS_AND_CHEMOTHERAPY%2C_55(4)%2C1661%2D1670%2C_2011[74].pdf
Banerjee, Antara and De, Manjarika and Ali, Nahid (2011) Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation. Antimicrobial Agents and Chemotherapy, 55 (4). pp. 1661-1670. |
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| Relation |
http://dx.doi.org/10.1128/AAC.00524-10
http://www.eprints.iicb.res.in/92/ |
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