Mr Kevin MATHA - nouveau docteur de l'Université d'Angers

The November 9, 2020

Formulation of innovative nanocarriers to treat visceral leishmaniasis

Directeur de Thèse: Pr Jean-Pierre Benoit

Co-directeur de Thèse: Pr Brice Calvignac

Abstract :

Visceral Leishmaniasis (VL) is a vector-borne anthropozoonosis caused by a unicellular parasitic protozoan of the Leishmania genus. Among the 20 Leishmania species responsible for human diseases, Leishmania donovani and Leishmania infantum are the two most important agents causing VL and are responsible for substantial health problems affecting 400,000 people per year. The disease is lethal if untreated, leading to the death of 30 - 40,000 people yearly and yet the world health organization classified this disease as neglected. In the present work, we proposed the formulation and evaluation of two new types of nanocarriers: the hyaluronic acid/poly-L-arginine nanocomplexes (NCs) associating pentamidine and the lipid nanocapsules loaded with miltefosine (LNCs). Both systems were formulated with a microfluidic device in a continuous process, and both systems were characterized in physicochemical terms. The evaluation of the NCs was pushed further with a freeze-drying and a thorough characterization using several techniques (dynamic light scattering, static light scattering, multi-angle light scattering, nanotracking analysis). Both systems were hemocompatible as they induced no hemolysis, a moderate to weak complement activation and an extremely low toxicity on macrophages. When assessed on a macrophage/leishmania co-culture model, both systems showed a good efficacy. NCs and LNCs are promising nanomedicines to treat leishmaniasis as they show good signs of potential efficacy, safety, and scale-up possibilities.

Keywords : Nanomedicines, Leishmania, microfluidics, hemocompatibility