Planta Med 2009; 75 - P-108
DOI: 10.1055/s-2009-1216546

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

PR Veerareddy 1, V Vobalaboina 1, N Ali 2
  • 1University College of Pharmaceutical Sciences, Warangal, Andhra Pradesh, India-5006 009
  • 2Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, West Bengal, India

Leishmaniasis is a complex of disease syndromes, caused by protozoan parasites of the genus Leishmania [1]. The aim of this study was 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 (5 mg/kg) of piperine, LN-P and LN-P-MAN was injected intravenously. Mice were sacrificed 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 ± 1.7 nm to 365 ± 4.7 nm 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 ± 0.04 mg/ml, respectively. The peak plasma concentrations 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 postinfection, respectively. Pharmacokinetics of piperine in lipid nanospheres showed a biexponential 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, et al. (2000), Trans R Soc Trop Med Hyg, 94: 465–471. [2] Stauber LA, et al. (1958), J Protozoal, 5: 269–273.