Antileishmanial Activity, Pharmacokinetics and Tissue Distribution Studies of Mannose Grafted Piperine Lipid Nano Spheres

Leishmaniasis is a complex of disease syndromes, caused by protozoan parasites of the genus Leishmania [1]. Present study was aimed to evaluate antileishmanial activity, pharmacokinetics and tissue distribution studies of mannose grafted piperine lipid nanospheres (LN-P-MAN) in BALB/c mice. Lipid nanospheres of piperine (LN-P) and LN-P-MAN were prepared by homogenization followed by ultrasonication. Particle size and Zeta potential were determined using Malvern Zeta Sizer. Antileishmanial activity of piperine, LN-P and LN-P-MAN was assessed in BALB/c mice infected with Leishmania donovani AG83 for 60 days. A single dose (5mg/kg) of piperine, LN-P and LN-P-MAN was injected intravenously. Mice were scarified after 15 days of treatment with piperine, LN-P, LN-P-MAN and Leishman Donovan Unit (LDU) is counted [2]. The size and Zeta potential were 196.0±1.7nm to 365±4.7nm and –35.6±0.2 mV to –44.3±0.8 mV respectively. The entrapment efficiency and drug content were 99.36±0.05 to 99.92±0.04% and 0.98±0.01 to 0.91±0.04mg/ml respectively. The peak plasma concentration of LN-P and LN-P-MAN were approximately 3 to 3.5 folds higher than piperine. Piperine reduced 36% and 35%, LN-P reduced 63% and 52%, while LN-P-MAN reduced 94% and 89% of parasite burden in liver and spleen after 15 days of post infection, respectively. Pharmacokinetics of piperine in lipid nanospheres showed a bi-exponential decline with significantly high AUC, lower rate of clearance and smaller volume of distribution in comparison with piperine. LN-P-MAN showed highly reduced parasite burden than piperine. References: [1] Boelaert M, Criel B, et al. (2000) Trans R Soc Trop Med Hyg 94: 465–471. [2] Stauber LA, Franchino EM et al. (1958)J Protozoal 5: 269–273.