Preprint / Version 1

Nanotized Curcumin and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

Authors

  • Brajendra Tiwari aDivision of Biochemistry, CSIR-Central Drug Research Institute, Janki-Puram Vistar, Lucknow, India
  • Richa Pahuja cNucleic Acids Research Lab, CSIR-Institute of Genomics and Integrative Biology, Delhi, India
  • Pradeep Kumar cNucleic Acids Research Lab, CSIR-Institute of Genomics and Integrative Biology, Delhi, India
  • Srikanta Rath bDivision of Toxicology, CSIR-Central Drug Research Institute, Janki-Puram Vistar, Lucknow, India
  • Kailash Gupta cNucleic Acids Research Lab, CSIR-Institute of Genomics and Integrative Biology, Delhi, India
  • Neena Goyal aDivision of Biochemistry, CSIR-Central Drug Research Institute, Janki-Puram Vistar, Lucknow, India

Keywords:

KEYWORDS: Leishmania donovani, oral nanoparticle-based formulation, curcumin, miltefosine, combination therapy, in vivo efficacy, nanocurcumin

Abstract

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 parasite Leishmania. In 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 a Leishmania donovani-hamster model. We developed an oral nanoparticle-based formulation of curcumin. Nanoformulation of curcumin alone exhibited significant leishmanicidal activity both in vitro and in vivo. In combination with miltefosine, it exhibited a synergistic effect on both promastigotes and amastigotes under in vitro conditions. The combination of these two agents also demonstrated increased in vivo leishmanicidal 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. KEYWORDS: Leishmania donovani, oral nanoparticle-based formulation, curcumin, miltefosine, combination therapy, in vivo efficacy, nanocurcumin

Author Biographies

Richa Pahuja, cNucleic Acids Research Lab, CSIR-Institute of Genomics and Integrative Biology, Delhi, India

eAcademy of Scientific and Innovative Research, Chennai, India

Kailash Gupta, cNucleic Acids Research Lab, CSIR-Institute of Genomics and Integrative Biology, Delhi, India

dDepartment of Biological Sciences and Bioengineering and Centre for Environmental Science and Engineering, Indian Institute of Technology, Kanpur, India

Neena Goyal, aDivision of Biochemistry, CSIR-Central Drug Research Institute, Janki-Puram Vistar, Lucknow, India

eAcademy of Scientific and Innovative Research, Chennai, India

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