title: Nanotized Curcumin and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis.
abstract: Leishmaniasis chemotherapy remains very challenging due to high cost of the drug and its associated toxicity and drug resistance, which develops over a period of time. Combination therapies (CT) are now in use to treat many diseases, such as cancer and malaria, since it is more effective and affordable than monotherapy. CT are believed to represent a new explorable strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasiteLeishmaniaIn the present study, we investigated the effect of a combination of a traditional Indian medicine (ayurveda), a natural product curcumin and miltefosine, the only oral drug for visceral leishmaniasis (VL) using aLeishmania donovani-hamster model. We developed an oral nanoparticle-based formulation of curcumin. Nanoformulation of curcumin alone exhibited significant leishmanicidal activity bothin vitroandin vivoIn combination with miltefosine, it exhibited a synergistic effect on both promastigotes and amastigotes underin vitroconditions. The combination of these two agents also demonstrated increasedin vivoleishmanicidal activity accompanied by increased production of toxic reactive oxygen/nitrogen metabolites and enhanced phagocytic activity. The combination also exhibited increased lymphocyte proliferation. The present study thus establishes the possible use of nanocurcumin as an adjunct to antileishmanial chemotherapy.
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Janki-Puram Vistar, Lucknow, India.
authors.forename: Brajendra
authors.initials: B
authors.lastname: Tiwari
authors.affiliation: Nucleic Acids Research Lab, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.|Academy of Scientific and Innovative Research, Chennai, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Pahuja
authors.affiliation: Nucleic Acids Research Lab, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Division of Toxicology, CSIR-Central Drug Research Institute, Janki-Puram Vistar, Lucknow, India.
authors.forename: Srikanta Kumar
authors.initials: SK
authors.lastname: Rath
authors.affiliation: Nucleic Acids Research Lab, CSIR-Institute of Genomics and Integrative Biology, Delhi, India.|Department of Biological Sciences and Bioengineering and Centre for Environmental Science and Engineering, Indian Institute of Technology, Kanpur, India.
authors.forename: Kailash Chand
authors.initials: KC
authors.lastname: Gupta
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Janki-Puram Vistar, Lucknow, India neenacdri@yahoo.com.|Academy of Scientific and Innovative Research, Chennai, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Goyal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D004338:Drug Combinations; D004351:Drug Resistance / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008515:Medicine, Ayurvedic; D053758:Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D010587:Phagocytosis / Q000187:drug effects; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D026361:Reactive Nitrogen Species / Q000819:agonists / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D004337:Drug Carriers; D004338:Drug Combinations; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D010767:Phosphorylcholine; C039128:miltefosine; D003474:Curcumin
keywords: Leishmania donovani; combination therapy; curcumin; in vivo efficacy; miltefosine; nanocurcumin; oral nanoparticle-based formulation