Veerareddy P R, Vobalaboina V, Nahid A
University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh, India.
Pharmazie. 2004 Mar;59(3):194-7.
Present studies are aimed to find out the utility of oil-in-water emulsions also known as lipid nanospheres (LN) or fat emulsions for delivering piperine for the treatment of visceral leishmaniasis. Lipid nanosphere formulations of piperine were prepared using soybean oil, egg lecithin, cholesterol, stearylamine and phosphatidylethanolamine distearylmethoxypolyethyleneglycol (DSPE-PEG) by homogenization followed by ultrasonication of oil and aqueous phases. Antileishmanial activity of all the formulations was assessed in BALB/c mice infected with Leishmania donovani AG83 for 60 days. A single dose (5 mg/kg) of piperine, or lipid nanospheres of piperine (LN-P), or lipid nanosphere of piperine with stearylamine (LN-P-SA) or pegylated lipid nanospheres of piperine (LN-P-PEG) was injected intravenously. Mice were sacrificed after 15 days of treatment with piperine or formulations and Leishman Donovan Unit (LDU) is counted. Toxicity of formulations and pure piperine was assessed in normal mice. The size distribution of formulations ranged from 200 to 885 nm. Piperine reduced the parasite burden in liver and spleen by 38% and 31% after 15 days post infection respectively. LN-P reduced the parasite burden in liver and spleen by 63% and 52% after 15 days post infection, respectively. LN-P-PEG reduced the parasite burden in liver and spleen by 78% and 75% after 15 days post infection, respectively. LN-P-SA reduced the parasite burden in liver and spleen by 90% and 85% after 15 days post infection, respectively. LN-P, LN-P-PEG, LN-P-SA treated mice did not show any significant changes in the serum levels of SGOT, ALP, creatinine and urea compared to normal mice. Stable and sterile formulations of lipid nanospheres of piperine were developed. A single dose of 5 mg/kg of lipid nanospheres of piperine could significantly reduce the liver and splenic parasite burden.
目前的研究旨在探究水包油乳液（也称为脂质纳米球（LN）或脂肪乳剂）在递送胡椒碱用于治疗内脏利什曼病方面的效用。通过将大豆油、蛋黄卵磷脂、胆固醇、硬脂胺和二硬脂酰甲氧基聚乙二醇磷脂酰乙醇胺（DSPE-PEG）进行均质化，随后对油相和水相进行超声处理，制备了胡椒碱的脂质纳米球制剂。在感染杜氏利什曼原虫AG83达60天的BALB/c小鼠中评估了所有制剂的抗利什曼活性。静脉注射单剂量（5毫克/千克）的胡椒碱、胡椒碱脂质纳米球（LN-P）、含硬脂胺的胡椒碱脂质纳米球（LN-P-SA）或聚乙二醇化胡椒碱脂质纳米球（LN-P-PEG）。在用胡椒碱或制剂治疗15天后处死小鼠，并计数利什曼多诺万单位（LDU）。在正常小鼠中评估制剂和纯胡椒碱的毒性。制剂的粒径分布范围为200至885纳米。感染后15天，胡椒碱分别使肝脏和脾脏中的寄生虫负荷降低了38%和31%。感染后15天，LN-P分别使肝脏和脾脏中的寄生虫负荷降低了63%和52%。感染后15天，LN-P-PEG分别使肝脏和脾脏中的寄生虫负荷降低了78%和75%。感染后15天，LN-P-SA分别使肝脏和脾脏中的寄生虫负荷降低了90%和85%。与正常小鼠相比，LN-P、LN-P-PEG、LN-P-SA处理的小鼠血清中的谷草转氨酶、碱性磷酸酶、肌酐和尿素水平未显示任何显著变化。开发了稳定且无菌的胡椒碱脂质纳米球制剂。单剂量5毫克/千克的胡椒碱脂质纳米球可显著降低肝脏和脾脏中的寄生虫负荷。
