Development of topical treatment for cutaneous leishmaniasis caused by Leishmania major in experimental animals

El‐On, Joseph; Jacobs, G.P.; Witztum, Eliezer; Greenblatt, Charles L.

doi:10.1128/aac.26.5.745

Cited by 106 publications

(47 citation statements)

References 10 publications

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“…For the past decade, the use of SLN as an alternative carrier for colloidal drug delivery c and d)), respectively, and for the L. tropica amastigote were 1600 μg/ml (panel 2 (f)), 750 μg/ml, and 400 μg/ml (panel 2 (g and h)). Considering the drug's EC 50 , PM-SLN formulations, as in the previous tests, were determined to have a greater inhibitory effect and a significant inhibition of amastigote propagation was observed when the SLN-PM formulation was used compared to PM Effectiveness of topical formulations of 15% PM and 10% urea was reported (9,45,46). Here, we evaluated the in vitro anti-leishmanial activity of PM-SLN formulation against two Leishmania species.…”

Section: Discussionmentioning

confidence: 99%

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica

et al. 2015

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Abstract. Leishmaniasis is a worldwide disease that leads to high mortality and morbidity in human populations. Today, leishmaniasis is managed via drug therapy. The drugs that are already in clinical use are limited to a number of toxic chemical compounds and their parasite drug resistance is increasing. It is therefore essential, in order to circumvent the current difficulties, to design a new anti-leishmanial drug treatment strategy. Besides producing new, active anti-leishmanial entities, another promising strategy could be developing novel delivery systems and formulations of the existing pharmaceutical ingredients to improve drug efficacy. In the present study, paromomycin sulfate (PM), as one of the promising antileishmanial drugs, was formulated in solid lipid nanoparticles (SLN), and its in vitro efficacy was investigated against different strains of Leishmania using a MTT test, Parasite-Rescue-Transformation-Assay, SYTO Green staining, and fluorescent microscope imaging. The results show that PM-loaded SLN is significantly more effective than PM in inhibiting parasite propagation (P<0.05) and that cytotoxicity of PM-SLN formulations is size dependent. According to our results, delivery of the drugs to the macrophages via nanoparticle utilization seems to be an accessible and practical approach.KEY WORDS: cutaneous leishmaniasis; drug delivery system; paromomycin sulfate; solid lipid nanoparticle.

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Section: Discussionmentioning

confidence: 99%

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica

et al. 2015

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“…PM, like all the aminoglycoside antibiotics, inhibits protein biosynthesis in sensitive organisms (1). PM ointments were shown to be effective in an experimental model of murine leishmaniasis (17,38,39). The results of most clinical trials showed an acceptable level of efficacy of PM for the treatment of CL, especially lesions caused by L. major (5,43).…”

Section: Vol 53 2009 Topical Liposomal Paromomycin For Leishmaniasimentioning

confidence: 99%

“…In 1984, El-On and colleagues (17) described the activity of 15% PM plus 12% methylbenzethonium chloride in soft paraffin and it was marketed in Israel, but clinical studies of this formulation reported that it induced local toxicity and was not well tolerated (2,13).…”

Section: Vol 53 2009 Topical Liposomal Paromomycin For Leishmaniasimentioning

confidence: 99%

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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“…Different formulations (mixture) of paromomycin ointments (15-20%) with/without MBCL (12%) or urea (10%) were introduced but the results were equivocal and were not convincing (Grogl et al, 1999;Arana et al, 2001b). Adding 12% concentration of benzethonium chloride, cetalkonium chloride or dimethyl sulfoxide, all incorporated in white soft paraffin, could effectively cure the disease or healed the lesion significantly in BALB/c mice (El-On et al, 1984). Although many trials were undertaken, it is very difficult to comparatively discuss them (Arana et al, 2001b).…”

Section: Paromomycinmentioning

confidence: 99%

Topical Treatment Modalities for Old World Cutaneous Leishmaniasis: A Review

2012

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Diagnosis and therapy of cutaneous leishmaniasis (CL) can be difficult due to the variability of the clinical pictures and resistance to therapy. There is no vaccine currently available for CL. The aim of the present review is to describe different topical treatment modalities for old world CL. The mainstays of treatment for old world CL are pentavalent antimony compounds which are administered parenterally or intralesionally. New topical treatment alternatives have been available within the past few years. Amongst several treatments used topically, physical therapies including cryotherapy, heat therapy and CO 2 laser are promising for the treatment of old world CL. Along with that, other randomized placebo controlled trials should be designed to find new effective therapeutic regimens.

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Development of topical treatment for cutaneous leishmaniasis caused by Leishmania major in experimental animals

Cited by 106 publications

References 10 publications

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica

Drug Targeting to Macrophages With Solid Lipid Nanoparticles Harboring Paromomycin: an In Vitro Evaluation Against L. major and L. tropica

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

Topical Treatment Modalities for Old World Cutaneous Leishmaniasis: A Review

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