Abstract
Lack of vaccine and increasing chemotherapeutic toxicities currently necessitate the development of effective and safe drugs against various forms of leishmaniases. We characterized the cellular stress induced by a novel curcumin analogue, HO-3867, encapsulated within the phosphatidylcholine-stearylamine (PC-SA) liposome for the first time against Leishmania. The liposomal formulation of HO-3867 (i.e., PC-SA/HO-3867) initiated oxidative stress-induced apoptosis in L. donovani, revealed by altered cell morphology, phosphatidylserine externalization, mitochondrial depolarization, intracellular lipid accumulation, and cell cycle arrest in promastigotes. Liposomal HO-3867 was observed to be a strong apoptosis inducer in L. donovani and L. major in a dose-dependent manner, yet completely safe for normal murine macrophages. Moreover, PC-SA/HO-3867 treatment induced L. donovani metacaspase and PARP1 activation along with downregulation of the Sir2 gene. PC-SA/HO-3867 arrested intracellular L. donovani amastigote burden in vitro, with reactive oxygen species (ROS) and nitric oxide (NO)-mediated parasite killing. These data suggest that liposomal HO-3867 represents a highly promising and non-toxic nanoparticle-based therapeutic platform against leishmaniasis inspiring further preclinical developments.
Highlights
Visceral leishmaniasis (VL) or kala-azar is one of the deadly systemic infections caused by Leishmania donovani/Leishmania infantum with estimated 200,000–400,000 new cases and more than 20,000–30,000 deaths per year [http://www.who.int/mediacentre/factsheets/fs375/en/]
HO-3867-entrapped PC-SA liposomes were developed by thinfilm rehydration method (De et al, 2018)
Much lower IC50 values of 10 and 12.5 μg/ml were obtained after exposure to PC-SA/HO-3867 in L. donovani and L. major, respectively
Summary
Visceral leishmaniasis (VL) or kala-azar is one of the deadly systemic infections caused by Leishmania donovani/Leishmania infantum with estimated 200,000–400,000 new cases and more than 20,000–30,000 deaths per year [http://www.who.int/mediacentre/factsheets/fs375/en/]. For evaluating inhibitory effects of free and liposomal HO3867 on intracellular amastigotes, RAW 264.7 cells (2 × 105 cells/ coverslip) were infected with log-phase promastigotes of L. donovani (in 1:10 ratio) for 4 h in RPMI 1640 medium supplemented with 10% FCS.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
