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 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.

Micellar curcumin improves the antibacterial activity of the alkylphosphocholines erufosine and miltefosine against pathogenicStaphyloccocus aureusstrains

“…One of the most successful possibilities to improve the aqueous solubility of CRM and to protect the molecule from rapid degradation is to encapsulate it in nano-delivery systems [47][48][49][50][51]. Nano-sized CRM has already been successfully combined with MLT for treatment of leishmaniosis; thus giving the combination promising perspectives [52].…”

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2019) Micellar curcumin improves the antibacterial activity of the alkylphosphocholines erufosine and miltefosine against pathogenic Staphyloccocusaureus strains, Biotechnology & Biotechnological Equipment, 33:1,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] ABSTRACT In the light of the emerging bacterial resistance to broad-spectrum antibiotics, the search for new antibacterial therapeutics and drug combinations is one of the most challenging topics nowadays. In the present study, we investigated for the first time the antibacterial and biofilm inhibitory effects of the third generation anticancer alkylphosphocholine (APC) erufosine against pathogenic Staphylococcus aureus strains in comparison to the prototype of this pharmacological class of drugs, miltefosine.

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Nanomedicines for Cutaneous Leishmaniasis

“…In this sense, a few studies have attempted to improve miltefosine and amphothericin B oral efficacy in VL models by encapsulation in nanosystems [58,59]. For example, PLGA nanoparticles have been used to increase the oral bioavailability of the immunomodulator curcumin and the efficacy of miltefosine in hamsters infected with L. donovani [60]. However, only a few studies in the literature have used different nanosystems to increase drug efficacy in CL.…”

Dear Role of Herbal Plants in Prevention and Treatment of Parasitic Diseases

“…Leishmaniasis has been classified into 3 types: Visceral Leishmaniasis (VL), Cutaneous Leishmaniasis (CL) and Mucocutaneous Leishmaniasis (ML). Of all these classes of Leishmaniasis, VL is fatal if left untreated (Tiwari et al 2017). The disease is mainly associated with low income population in Africa, Asia and Latin America.…”