Combination Therapy Using Sodium Antimony Gluconate in Stearylamine-Bearing Liposomes against Established and Chronic<i>Leishmania donovani</i>Infection in BALB/c Mice

Pal, Swati; Ravindran, Rajesh; Ali, Nahid

doi:10.1128/aac.48.9.3591-3593.2004

Cited by 39 publications

(35 citation statements)

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“…Previously we showed the antileishmanial activity of PC-SA as monotherapy (2,14) as well as combination therapy (7,38). Here, the efficacy of these leishmanicidal liposomes was determined as a delivery tool, as well as in combination with PM.…”

Section: Resultsmentioning

confidence: 99%

“…Earlier we established the leishmanicidal activity and mechanism of the cationic liposome, composed of phosphatidylcholine (PC) and stearylamine (SA), as a monotherapy (2,6,14). PC-SA in combination with other antileishmanial drugs, such as SAG and AmB, not only reduced the toxicity of the drugs but also enhanced the parasite clearance in the BALB/c model to a great extent (7,38). Moreover, beneficial immunomodulatory activities of AmB were augmented in combination with PC-SA liposomes (7).…”

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confidence: 99%

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Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation

Banerjee

Ali

2011

Antimicrob Agents Chemother

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation

Banerjee

Ali

2011

Antimicrob Agents Chemother

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“…The highest concentrations of drugs used were 90% effective doses for the suppression of parasite infection in macrophages and nontoxic to cells (Ref. 53; D. Banerjee and N. Ali, unpublished observations). It was found that both SAG and AmB were able to downregulate the enhanced production of IL-10 stimulated by LPS in a dose-dependent manner (Fig.…”

Section: Ability Of Sag and Amb To Modulate Cytokine Production Of Humentioning

confidence: 99%

IL-10- and TGF-β-Mediated Susceptibility in Kala-azar and Post-kala-azar Dermal Leishmaniasis: The Significance of Amphotericin B in the Control of Leishmania donovani Infection in India

Saha

Mondal

Ravindran

et al. 2007

The Journal of Immunology

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Visceral leishmaniasis (VL) or kala-azar is known to be associated with a mixed Th1-Th2 response, and effective host defense requires the induction of IFN-γ and IL-12. We address the role of the differential decline of IL-10 and TGF-β in response to sodium antimony gluconate (SAG) and amphotericin B (AmB), the therapeutic success of SAG and AmB in Indian VL, and the significance of IL-10 and TGF-β in the development and progression of post-kazla-azar dermal leishmaniasis (PKDL). In the active disease, PBMC from VL patients showed suppressed Ag-specific lymphoproliferation, IFN-γ and IL-12 production, and elevation of IL-10 and TGF-β. Cure corresponded with an elevation in IFN-γ and IL-12 production and down-regulation of IL-10 and TGF-β. Both CD4+ and CD8+ T cells were involved in IFN-γ and IL-10 production. Interestingly, the retention and maintenance of residual IL-10 and TGF-β in some SAG-treated individuals and the elevation of IL-10 and TGF-β in PKDL, a sequel to kala-azar, probably reflects the role of these cytokines in reactivation of the disease in the form of PKDL. Contrastingly, AmB treatment of VL resulted in negligible TGF-β levels and absolute elimination of IL-10, reflecting the better therapeutic activity of AmB and its probable role in the recent decline in PKDL occurrences in India. Moreover, elucidation of immune responses in Indian PKDL patients revealed a spectral pattern of disease progression where disease severity could be correlated inversely with lymphoproliferation and directly with TGF-β, IL-10, and Ab production. In addition, the enhancement of CD4+CD25+ T cells in active VL, their decline at cure, and reactivation in PKDL suggest their probable immunosuppressive role in these disease forms.

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“…In the proper formulations and at the appropriate sizes, liposomes deliver drugs to the skin on the basis of the similarity of the bilayer structure of the lipid vesicles to that of the natural membrane and target the macrophages within the dermis (6, 7, 41). Several lipidbased formulations for the treatment of experimental leishmaniasis have been developed (11,19,40,45). …”

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Effect of Topical Liposomes Containing Paromomycin Sulfate in the Course of Leishmania major Infection in Susceptible BALB/c Mice

Jaafari

Bavarsad

Bazzaz

et al. 2009

Antimicrob Agents Chemother

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The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomycin sulfate (PM) in Leishmania major-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37°C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against L. major promastigotes in culture were 65.32 and 59.73 g/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 g/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P < 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (P < 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.Leishmaniasis, which has diverse clinical manifestations, is caused by different species of Leishmania and is endemic in many countries (49). Although cutaneous leishmaniasis (CL) is a self-healing disease, healing takes a long time, and healing times of even up to 2 years have been reported (37). Pentavalent antimonials, which are still the first-line treatment for CL, require multiple injections and are painful; as such, they are not tolerated by most of the patients and, moreover, are not always effective. In addition, resistance to pentavalent antimonials has been reported (12,13,33).Paromomycin sulfate (PM) was reported to show anti-Leishmania activity in the 1960s, and since then PM showed promising activity against both CL and visceral leishmaniasis (VL) in clinical trials (13, 31). Recently, the parenteral formulation of PM has been approved for use for the treatment of VL (27). Nevertheless, the systemic use of PM might cause nephrotoxicity. The conventional topical dosage forms of PM have been tested in clinical trials for their activities against CL and showed promising results, but acceptable efficacy was not always seen (2,3,5,13,18,23,28,43). The formidable barrier nature of the stratum corneum (SC) of the skin does not allow the penetration of drugs with high hydrophilicities and molecular weights, like PM (19). Furthermo...

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Combination Therapy Using Sodium Antimony Gluconate in Stearylamine-Bearing Liposomes against Established and ChronicLeishmania donovaniInfection in BALB/c Mice

Cited by 39 publications

References 35 publications

Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation

Combination Therapy with Paromomycin-Associated Stearylamine-Bearing Liposomes Cures Experimental Visceral Leishmaniasis through Th1-Biased Immunomodulation

IL-10- and TGF-β-Mediated Susceptibility in Kala-azar and Post-kala-azar Dermal Leishmaniasis: The Significance of Amphotericin B in the Control of Leishmania donovani Infection in India

Effect of Topical Liposomes Containing Paromomycin Sulfate in the Course of Leishmania major Infection in Susceptible BALB/c Mice

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