In vitroanalysis regarding the safety of components used in a film-based therapeutic system loaded with meglumine antimoniate and its activity towardLeishmania majorexperimental infections: a preliminary study

Abstract

Owing to its biocompatibility properties and its ability to promote the scar healing process, chitosan is employed in tissue engineering for the manufacture of formulations. To control the characteristic skin ulcers of cutaneous leishmaniasis (CL), the use of a biopolymeric system that favors the scar healing process and releases an active agent such as meglumine antimoniate may be a better option. For these reasons, here we analyzed the cytotoxic capabilities of excipients [medium molecular weight chitosan (MMWC), lactic acid (LA) and polyvinylpyrrolidone (PVP)], used for the formulation of a film-based therapeutic system that releases meglumine antimoniate and were evaluated on human macrophages [monocyte-derived macrophages (MDMs)], L929 fibroblasts and parasites (Leishmania major promastigotes and intracellular amastigotes). The ability of excipients to modulate the cytokines production involved in the scar healing process was compared with film-based therapeutic system. The efficiency of a film-based therapeutic system loaded with meglumine antimoniate was compared with conventional formulation (Albiventriz(®)). We found that MMWC was toxic for two parasite forms. In contrast, measurement of interleukin levels did not show any evidence of preferential secretion as a side effect of treating human macrophages with MMWC. Finally, the efficiency of a polymeric film-based therapeutic system that was loaded with meglumine antimoniate could not be determined due to the high degree of toxicity observed in infected MDMs; moreover, these compounds do not induce any apparent immunomodulatory effects. Our findings suggest that the final concentrations of each excipients (MMWC, LA and PVP) that were used in the polymeric film were suitable vehicles for active pharmaceutical compound delivery and did not selectively affect (enhancing or diminishing immune activity) macrophages.

Acid heteropolysaccharides with potent antileishmanial effects

“…Accordingly, galactomannan (GMPOLY) isolated from lichen Ramalina celastri and an arabinomannose (Z-100) extracted from Mycobacterium tuberculosis have been classified as macrophage activators exhibiting leishmanicidal effect in vitro [17,18]. The use of the chitosan polymer as a vehicle in the preparations of meglumine antimoniate or doxorubicin for experimental leishmaniasis treatment has been investigated and promising results has been observed [19,20]. Recently, mannose-conjugated chitosan nanoparticles loaded with rifampicin, aiming a selective delivery of rifampicin for the treatment of visceral leishmaniasis has been investigated [21].…”