P-toluenesulfonychloride-based niosomes for Amphotericin-B against Leishmaniasis

Abstract

Nonionic-surfactants have been reported as nanocarriers for delivering low bioavailable drugs at the target sites. In the current study, two new nonionic surfactants were synthesized to enhance the oral bioavailability of the low water-soluble antifungal drug Amphotericin-B. The hemolysis effect of nonionic surfactants on red blood cells and cytotoxicity against the 3T3 cell line was studied. Both surfactants have shown low hemolysis and cytotoxicity as compared to standard Tween 80. The morphology of drug-loaded niosomes of nonionic surfactants 1 and 2 was studied by using atomic force microscopy (AFM), and both surfactants based vesicles were spherical, while their average sizes were measured by dynamic light scattering (DLS). The average size, zeta potential and polydispersity index (PDI) values of surfactants 1 and 2 were 282 ± 3 nm, −8 ± 1 mV, 0.26 and 287 ± 3 nm, −10 ± 1 mV, 0.24. The drug entrapment efficiency and critical micelle concentrations of nonionic surfactants were determined by using UV–visible spectroscopy. The structures of surfactants 1 and 2 were assessed through single-crystal x-ray crystallographic analysis, while Hirshfeld analysis was performed to study the intermolecular interactions of molecules, as well as the packing behavior of their crystals. The nonionic-surfactant 1 was further tested for antileishmanial activity against Leishmania tropica promastigotes, in both drug-loaded and unloaded niosomal vesicular forms. The nonionic surfactant 1 was found to be a potentanti-leishmanial agent in the drug-loaded form with IC₅₀ = 3.02 ± 0.91 μM in comparison to their standard drugs Amphotericin-B (IC₅₀ = 3.8 ± 0.04 μM) and miltefosine (IC₅₀ = 42.2 ± 0.6 μM) (p < 0.1). These results, therefore, form the basis of further results towards efficient drug delivery against tropical disease Leishmaniasis.