The active ingredient in turmeric, curcumin, has been used in traditional Indian medicine as a therapeutic for centuries. Its anti-cancer, anti-infectious and anti-inflammatory properties have been proved by modern medicine.
However, curcumin does not dissolve fully in water, and so is not absorbed by cells -- it has low “bioavailability”. A group of researchers from IISc, Bose Institute Kolkatta and the University of Pune have devised a method that pulverizes curcumin to convert it to nanoparticles 20-50 nanometres in diameter. This “nanotised” curcumin is then delivered orally as a form of antimalarial therapy.
Curcumin has been shown to have anti-parasite effects, with protozoans like Leishmania, Trypanosoma, Giardia and malaria-causing Plasmodium falciparum. Malaria parasites live in the red blood cells after onset of infection; clearing them out usually involves using drugs like artemisinin. Nanoparticle based malaria therapy has been explored before, because there is the advantage of improving interaction with infected red blood cells. But, there have been issues with safety and biocompatibility.
The “nanotised” curcumin developed in this study have been shown to effectively treat malaria infested mice. In experiments conducted with mice infected with Plasmodium berghei, a relative of malaria causing Plasmodium falciparum and P. vivax, mice treated with nanotised curcumin survived for 34 days, and the parasites were cleared from their blood. Mice treated with native curcumin could only survive for 22 days.
When treatment was continued with nanotised curcumin, mice survived for more than two months, and almost 50% were completely cured. Onset of pathological symptoms like ataxia, convulsions, and hypothermia was much delayed when nanotised curcumin was used.
These nanotised curcumin particles are also independent of a “carrier” – most other drug delivery systems use a polymer as a carrier to take them to desired locations in the body. The procedure allows it to disperse in water, while natural curcumin is only soluble in organic solvents. This increased the bioavailability of nanotised curcumin, compared to that of native curcumin. The dried curcumin can also be stored for a year without any decomposition.
The nanotised curcumin had a higher uptake, and could be detected in blood plasma of mice at higher levels than native curcumin. Release of curcumin also occurred in a controlled manner, with 50% of the drug released by 24 hours and curcumin still retained after 48 hours. It was also highly effective – it could wipe out parasites at one-tenth the concentration of native curcumin.
Conventional chemotherapy for malaria requires ever-higher doses because the parasites develop drug resistance. Using intracellular drug delivery mechanisms deals with this issue by maintaining high concentrations of the drug within the red blood cells. Nanotised curcumin, delivered orally in this study, has striking therapeutic potential and the methodology followed can also be potentially used to nanotise other natural substances.
About the authors:
Aparajita Ghosh and Suman Bhandary are at the Division of Molecular Medicine, Bose Institute, Kolkata. Tanushree Banerjee is at the Department of Biotechnology, University of Pune. Avadhesha Surolia is a Professor at the Molecular Biophysics Unit, Indian Institute of Science, Bangalore.
The paper appeared in the International Journal of Nanomedicine on 20th November 2014.