Topical treatment with nanoliposomal Amphotericin B reduces early lesion growth but fails to induce cure in an experimental model of cutaneous leishmaniasis caused by Leishmania mexicana.

Leishmania mexicana infection causes localized skin lesions that can lead to tissue damage and permanent disfigurement if not resolved. Currently, recommended treatments include intravenous administration of Amphotericin B, which is undesirable due to the associated cost and patient burden related to receiving regular injections. In this study, we evaluated the effect of topical treatment with a nanoliposomal formulation of Amphotericin B that is penetrable to the skin (SinaAmphoLeish 0.4%) in mice infected with L. mexicana by using ulcerated (BALB/c) and non-ulcerated (129SVE) models. BALB/c mice received a 4 week treatment following ulcerated lesion development, while 129SVE mice received a 10 week treatment beginning at week 5 post-infection. Although mice from both models showed comparable susceptibility to L. mexicana infection after topical treatment with SinaAmphoLeish relative to controls, 129SVE mice displayed a transient decrease in lesion sizes which eventually became similar to control mice. On other hand this treatment resulted in no reduction in the lesion sizes in BALB/c mice. 129SVE treated mice exhibited greater IFN-γ, IL-4, and IL-10 cytokine levels and higher T-cell proliferation in re-stimulated draining lymph node cells. BALB/c mice showed no differences in cytokine responses between treated and control mice. These findings indicate that topical SinaAmphoLeish treatment is not likely to be effective in the treatment of cutaneous leishmaniasis caused by L. mexicana.

Immunomodulatory and Antileishmanial Activity of Phenylpropanoid Dimers Isolated from Nectandra leucantha.

Three phenylpropanoid dimers (1-3) including two new metabolites were isolated from the extract of the twigs of Nectandra leucantha using antileishmanial bioassay-guided fractionation. The in vitro antiparasitic activity of the isolated compounds against Leishmania donovani parasites and mammalian cytotoxicity and immunomodulatory effects were evaluated. Compounds 1-3 were effective against the intracellular amastigotes within macrophages, with IC50 values of 26.7, 17.8, and 101.9 µM, respectively. The mammalian cytotoxicity, given by the 50% cytotoxic concentration (CC50), was evaluated against peritoneal macrophages. Compounds 1 and 3 were not toxic up to 290 µM, whereas compound 2 demonstrated a CC50 value of 111.2 µM. Compounds 1-3 also suppressed production of disease exacerbatory cytokines IL-6 and IL-10 but had minimal effect on nitric oxide production in L. donovani-infected macrophages, indicating that antileishmanial activity of these compounds is mediated via an NO-independent mechanism. Therefore, these new natural products could represent promising scaffolds for drug design studies for leishmaniasis.