Efficacy of topical Risedronate against Leishmania amazonensis in vivo

GUZMAN MARIA LAURA; MARIA E OLIVERA ME; PERALTA FLORENCIA; MARCO J. DIEGO; BARROSO PAOLA; BRACAMONTE MA. ESTEFANIA; CARRER, DOLORES

Congreso; Drug Discovery for Neglected Diseases International Congress 2018 4th Scientific Meeting of ResNet NPND; 2018

Introduction: Cutaneous Leishmaniasis (CL) is the most prevalent form of Leishmaniasis in the world. It is also the most important form in South America. A topical treatment is attractive because of the potential to diminish side effects, increase patient compliance, ease of use in rural contexts and affordability. Biphosphonates and the polyelectrolyte Eudragit E100 (EuE100) have shown to be active against some forms of Leishmania (Rodriguez et al. 2002, Docampo et al. 2001, Yardley et al. 2002, Serrano et al 2017). Objectives: To compare the efficacy of a topical treatment containing Risedronate (Ris) or complexed Ris (EuE100-Ris, Guzman et al. 2016) on an animal model of Cutaneous Leishmaniasis.Materials and Methods: We used Balb/c mice. The animals were injected with L. amazonensis promastigotes intradermally in the base of the tail. Ris and EuE100-Ris (dose??) were incorporated in a hydrogel and applied either once or twice daily for 21 days. To evaluate efficacy and toxicity we performed measurements of lesions size and evaluated lesions appearance/necrosis. Remaining parasites were determined by MTT. Levels of anti-Leishmania IgG1 and IgG2a and GOT and GPT enzymes were determined from serum. Results: Ris started to reduce the lesions size 15 days after the beginning of the treatment, while EuE100-Ris reduced it from the first day of treatment. Ris flattened the edges of the lesions and closed the ulcers in 63 % of animals. The complex with EuE100 increased this efficacy to 80 % of animals. The number of remaining parasites in the lesions was 87 % in the animals treated with Ris and 27 % in the animals treated with Eu100-Ris. In both groups the IgG2a levels showed a tendency to a cure and GOT and GPT levels were normal.Discussion: topical Ris produced a slight discomfort in the animals upon application on the ulcer. This should be taken into account when developing a further formulation. Conclusions: Topical Ris showed efficiency eliminating ulcers caused by L. (L.) amazonensis in mice. The complex Eu100-Ris enhanced this result and further reduced the parasitic burden. No hepatic damage was detected. The results are promising and the system should be enhanced to reach total parasite elimination.