Combination of amphotericin B and chitosan platelets for the treatment of experimental cutaneous leishmaniasis: Histological and immunohistochemical examinations

Abstract

Cutaneous leishmaniasis (CL) is a chronic infectious disease caused by protozoa of the genus Leishmania. Although amphotericin B-deoxycholate (AmB-DOC) showed its ability to partially cure the infection after intravenous administration, it can lead to dose-limiting side-effects (mainly nephorotoxicity). Previous data from our group showed that chitosan particles with typical flat surfaces, called platelets acted as a booster of AmB-DOC activity against Candida albicans and C. glabrata. Platelets were obtained by a hierarchical self-assembly process between chitosan hydrophobically-modified with oleic acid and α-cyclodextrin in water. The objective of this work is to investigate whether chitosan platelets are active against CL, alone or in combination with AmB-DOC. In vitro evaluations showed that platelets exhibited intrinsic antiparasitic activity, while native chitosan was inactive. When combined with AmB-DOC, chitosan platelets exerted an additive effect against Leishmania major amastigote (Fractional inhibitory concentration index FICI = 1.213). Histological and immunohistochemical examinations of skin lesions of mice infected with L. major and treated with the combination showed a significant decrease of the inflammatory granuloma and a reduction of the parasitic load, in comparison with AmB-DOC alone. Our work provides histological and immunohistochemical evidences that the combination of chitosan platelets and AmB could be considered as a strategy to cure CL.