Cutaneous leishmaniasis: new oral therapeutic approaches under development

Abstract

The World Health Organization (WHO) classifies leishmaniasis as a disease for which the development of new treatments is a priority. Available drugs are not fully effective in all cases; they have parenteral administration and exhibit serious and common adverse effects. The only oral drug available (miltefosine) has shown resistance, is expensive, and is not available in many endemic countries. Thus, the development of an oral medicine may solve many of these issues. Based on that, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs for the treatment of cutaneous leishmaniasis. A literature search for keywords “leishmania and oral” was performed in PubMed and ScienceDirect, considering articles published in the last 5 years. The articles were selected based on the objective of the review. The main problem in the current treatment of leishmaniasis is the administration of injectables, since it requires patients to travel to health centers, hospitalization, and professional administration, conditions that are not adapted to the socioeconomic reality of patients. Therefore, many research studies have evaluated oral alternatives for the treatment of cutaneous leishmaniasis. The main tested approaches were obtaining new molecules, repositioning drugs, and new formulations of old drugs. The prospects are encouraging but still require more in vivo bioavailability and clinical trials.

The Possible Role of Selected Vitamins and Minerals in the Therapeutic Outcomes of Leishmaniasis

“…Available drugs are not always completely effective; they require i.v administration and also have common and serious side effects. Miltefosine is the only oral drug that is effective against leishmaniasis; however, it has some drawbacks, including resistance, high cost, and non-availability in several endemic regions [120]. As a result, investigating therapeutic alternatives to develop an oral medicine could overcome most of these problems.…”

Synthesis and Evaluation of (Bis)benzyltetrahydroisoquinoline Alkaloids as Antiparasitic Agents

“…Leishmaniases are a group of protozoan neglected diseases caused by over 20 species of the Leishmania genus that are transmitted via infected sandflies and affect roughly 12 million people worldwide. , The wide range of clinical manifestations, asymptomatic cases, and poor diagnosis suggests that the incidence numbers are likely significantly higher than estimated . Visceral leishmaniasis (VL), the most severe form of the disease, is caused by Leishmania donovani and Leishmania infantum and is lethal unless treated, with up to 65,000 deaths annually, thus being the deadliest parasitic disease after malaria .…”

“…18 Many alkaloids in this family have been investigated due to their interesting pharmacological profiles, including antimicrobial and anticancer properties. 19,20 Macrocyclic BBIs have been sporadically investigated as antiparasitic agents over the last half century, with alkaloids such as northalrugosidine (2) and daphnandrine (3) shown to be active against extracellular L. donovani promastigotes and T. cruzi epimastigotes, respectively. 21−25 However, since much of this work has been performed on the readily cultured extracellular insect life cycle stages of the parasites, relying on simpler assays that in the case of neglected tropical diseases rarely yield viable drug candidates, BBIs remain to be rigorously investigated as potential antiparasitic agents.…”

“… 1 , 2 The wide range of clinical manifestations, asymptomatic cases, and poor diagnosis suggests that the incidence numbers are likely significantly higher than estimated. 3 Visceral leishmaniasis (VL), the most severe form of the disease, is caused by Leishmania donovani and Leishmania infantum and is lethal unless treated, with up to 65,000 deaths annually, 4 thus being the deadliest parasitic disease after malaria. 5 The fatality of the disease is attributed to the parasite spreading to and irreversibly damaging vital organs such as the liver, spleen, and bone marrow.…”

Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment

“…These drugs have limitations such as low efficacy, the potential development of resistance, parenteral administration, and the need for hospitalization, making adherence difficult and increasing related costs. In addition, these treatments can cause serious side effects, such as hematological, pancreatic, and cardiac toxicity and teratogenicity [ 4 ]. The World Health Organization (WHO) recommends the investigation of alternative drugs and topical (local) and systemic (oral) formulations.…”