Therapeutic activity of a topical formulation containing 8-hydroxyquinoline for cutaneous leishmaniasis

Cutaneous leishmaniasis exhibits a wide spectrum of clinical manifestations, however, only a limited number of drugs are available and include Glucantime® and amphotericin B, which in patients induce unacceptable side effects, limiting their use. Thus, there is an urgent demand to develop a treatment for leishmaniasis. Recently, it was demonstrated that 8-hydroxyquinoline (8-HQ) showed significant leishmanicidal effects in vitro and in vivo. Based on it, this work aimed to develop a topical formulation containing 8-HQ and assess its activity in experimental cutaneous leishmaniasis. 8-HQ was formulated using Beeler base at 1 and 2% and showed an emulsion size with a D50 of 25 and 51.3 µm respectively with a shear-thinning rheological behaviour. The creams were able to permeate artificial Strat-M membranes and excised porcine skin without causing any morphological changes in porcine skin or murine skin tested. In BALB/c mice infected with L. (L.) amazonensis, topical treatment with creams containing 1 or 2% of 8-HQ was found to reduce parasite burden and lesion size compared to infected controls with comparable efficacy to Glucantime® (50mg/kg) administered at the site of cutaneous lesion. In the histological section of the skin from infected controls, a diffuse inflammatory infiltrate with many heavily infected macrophages that were associated with areas of necrosis was observed. On the contrary, animals treated with both creams showed only moderate inflammatory infiltrate, characterized by few infected macrophages, while tissue necrosis was not observed. These histological characteristics in topically treated animals were associated with an increase in the amount of IFN- γ and a reduction in IL-4 levels. The topical use of 8-HQ was active in decreasing tissue parasitism and should therefore be considered an interesting alternative directed to the treatment of leishmaniasis, considering that this type of treatment is noninvasive, painless, and, importantly, does not require hospitalization, improving patient compliance by allowing to conduct the treatment