Title:Innovative Lead Compounds and Formulation Strategies As Newer Kinetoplastid Therapies
Volume: 19
Issue: 25
Author(s): S. Espuelas, D. Plano, P. Nguewa, M. Font, J.A. Palop, J.M. Irache and C. Sanmartin
Affiliation:
Keywords:
Chagas disease, chemotherapy, human African trypanosomiasis, drug delivery systems, leishmaniasis, oral administration, selenium derivatives, protozoan diseases leishmaniasis, nanomedicines
Abstract: The protozoan diseases leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease (CD) are responsible for
substantial global morbidity and mortality in tropical and subtropical regions. Environmental changes, drug resistance and immunosuppression
are contributing to the emergence and spread of these diseases. In the absence of safe and efficient vaccines, chemotherapy, together
with vector control, remains the most important measure to control kinetoplastid diseases. Nevertheless, the current chemotherapeutic
treatments are clearly inadequate because of their toxic effects, generation of resistances as well as route and schedules of administration
not adapted to the field-conditions. This review overlooks the strategies that can be addressed to meet immediately the patient
needs such as the reconsideration of current regimens of administration and the rational combination of drugs in use. In the medium-long
term, due to new methodologies of medicinal-chemistry, the screening from natural products and the identification of new therapeutic
targets, new lead compounds have great chance to advance through the drug development pipeline to clinic. Modern pharmaceutical formulation
strategies and nanomedicines also merit a place in view of the benefits of a single dose of liposomal Amphotericin B (AmBisome
®) against visceral leishmaniasis. BBB-targeted nanodevices could be suited for selective delivery of drugs against HAT encephalitic
phase. Bioadhesive nanoparticles can be proposed to enhance the bioavailability of drugs after oral administration by reason of improving
the drug solubility, and permeability across the intestinal epithelia.
