Kolenyak-Santos Fernanda, Garnero Claudia, de Oliveira Rosimeire N, de Souza Ana L R, Chorilli Marlus, Allegretti Silmara M, Longhi Marcela R, Chaud Marco V, Gremião Maria P D
J Nanosci Nanotechnol. 2015 Jan;15(1):761-72. doi: 10.1166/jnn.2015.9186.
Praziquantel (PZQ) is a pyrazinoisoquinoline anthelmintic that was discovered in 1972 by Bayer Germany. Currently, due to its efficacy, PZQ is the drug of choice against all species of Schistosoma. Although widely used, PZQ exhibits low and erratic bioavailability because of its poor water solubility. Nanostructured lipid carriers (NLC), second-generation solid lipid nanoparticles, were developed in the 1990s to improve the bioavailability of poorly water soluble drugs. The aim of this study was to investigate nanostructured lipid carriers as a strategy to improve the efficacy of PZQ in S. mansoni treatment. We prepared NLC2 and NLC4 by adding seventy percent glycerol monostearate (GMS) as the solid lipid, 30% oleic acid (OA) as the liquid lipid and two surfactant systems containing either soybean phosphatidylcholine/poloxamer (PC/P-407) or phosphatidylcholine/Tween 60 (PC/T60), respectively. The carriers were characterized by nuclear magnetic resonance, differential scanning calorimetry, thermogravimetric analysis and Fourier transform-infrared spectroscopy. The safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. The results showed that the encapsulation of PZQ in NLC2 or NLC4 improved the safety profile of the drug. Treatment efficacy was evaluated on the S. mansoni BH strain. PZQ-NLC2 and PZQ-NLC4 demonstrated an improved efficacy in comparison with free PZQ. The results showed that the intestinal transport of free PZQ and PZQ-NLC2 was similar. However, we observed that the concentration of PZQ absorbed was smaller when PZQ was loaded in NLC4. The difference between the amounts of absorbed PZQ could indicate that the presence of T60 in the nanoparticles (NLC4) increased the rigid lipid matrix, prolonging release of the drug. Both systems showed considerable in vitro activity against S. mansoni, suggesting that these systems may be a promising platform for the administration of PZQ for treating schistosomiasis.
吡喹酮（PZQ）是一种吡嗪异喹啉类驱虫药，由德国拜耳公司于1972年发现。目前，由于其疗效显著，PZQ是治疗所有血吸虫种类的首选药物。尽管广泛使用，但由于其水溶性差，PZQ的生物利用度较低且不稳定。纳米结构脂质载体（NLC），即第二代固体脂质纳米粒，于20世纪90年代开发出来，以提高水溶性差的药物的生物利用度。本研究的目的是研究纳米结构脂质载体作为提高PZQ治疗曼氏血吸虫疗效的一种策略。我们通过添加70%的硬脂酸甘油酯（GMS）作为固体脂质、30%的油酸（OA）作为液体脂质以及分别含有大豆磷脂酰胆碱/泊洛沙姆（PC/P - 407）或磷脂酰胆碱/吐温60（PC/T60）的两种表面活性剂体系来制备NLC2和NLC4。通过核磁共振、差示扫描量热法、热重分析和傅里叶变换红外光谱对载体进行了表征。使用红细胞溶血和体外细胞毒性试验评估了安全性。结果表明，PZQ包封在NLC2或NLC4中可改善药物的安全性。在曼氏血吸虫BH株上评估了治疗效果。与游离PZQ相比，PZQ - NLC2和PZQ - NLC4表现出更高的疗效。结果表明，游离PZQ和PZQ - NLC2的肠道转运相似。然而，我们观察到当PZQ负载在NLC4中时，吸收的PZQ浓度较小。吸收的PZQ量之间的差异可能表明纳米粒（NLC4）中T60的存在增加了刚性脂质基质，延长了药物的释放。两种体系对曼氏血吸虫均表现出相当的体外活性，表明这些体系可能是用于施用PZQ治疗血吸虫病的有前景的平台。
