Hexadecylphosphocholine (Miltefosine) stabilized chitosan modified Ampholipospheres as prototype co-delivery vehicle for enhanced killing of L. donovani.

Lipid nanoparticles are stable, biodegradable and biocompatible carriers offering excellent therapeutic efficacy. Here, a novel effort has been made to develop Miltefosine (HePC- hexadecylphosphocholine) stabilized chitosan anchored nanostructured lipid carriers (NLC) of Amphotericin B (AmB) as co-delivery vehicle to enhance killing of L. donovani. The entrapment efficiency of AmB was achieved upto 85.3% for HePC-AmB-CNLCs with mean particle size of 150.8±8.4nm, and zeta potential value of +28.2±1.1mV, respectively. The cumulative amount of AmB released at even after the 24h was less than 65% from HePC-AmB-CNLCs and Tween-80-AmB-CNLCs. Intravenous administration of HePC-AmB-CNLCs revealed the significantly increased localization of AmB in both liver and spleen when estimated. FACS study represented enhanced uptake of FITC-HePC-CNLCs over FITC-HePC-NLCs in J774A.1 cell lines. Highly significant in vitro and in vivo anti-leishmanial activity (p<0.05 compared with Tween 80-AmB-CNLCs) was observed with HePC-AmB-CNLCs when tested against VL in Leishmania donovani-infected hamsters. The haemolysis and cytotoxicity studies showed the safety of HePC-AmB-CNLCs and Tween 80-AmB-CNLCs. The findings suggested that it would be preferable to deliver AmB through HePC stabilized chitosan anchored nanostructured lipid carriers for rapid and effective treatment with decreased adverse effects.