Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: Pharmacokinetic and pharmacodynamic evaluation
Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: Pharmacokinetic and pharmacodynamic evaluation
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DOI：
10.1016/j.ejpb.2016.10.022
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发表时间：
2017-01-01
影响因子：
4.9
通讯作者：
Veerabrahma, Kishan
中科院分区：
文献类型：
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作者：
Dudhipala, Narendar;Veerabrahma, Kishan
本研究的目的是通过固体脂质纳米颗粒 (SLN) 改善瑞舒伐他汀钙 (RC) 的药代动力学 (PK) 和药效 (PD) 效果。 RC是抗高血脂药物，由于首过代谢，口服生物利用度较低（20%）。以硬脂酸、山嵛酸甘油酯和三月桂酸甘油酯为脂质基质，鸡蛋卵磷脂和泊洛沙姆188为表面活性剂，采用热均质超声法制备RC-SLNs。测试制备的 SLN 的粒径、PDI、zeta 电位 (ZP)、包封率 (EE)、药物含量和体外释放。此外，对选定的 SLN 进行了 PLC 和 PD 研究。优化后的 SLN 在冷藏和室温下 90 天的物理稳定性没有变化。用三月桂酸甘油酯制备的SLN具有67.21+/-1.71nm的平均尺寸、0.25+/-0.01的PDI、-28.93+/-0.84mV的ZP和93.51+/-0.34%EE被认为是优化的。 DSC 和 XRD 研究表明药物和脂质之间没有发生相互作用。 SEM 和 TEM 研究表明 SLN 的形状接近球形。 PK 研究表明，与悬浮液相比，SLN 的口服生物利用度（吸收程度）提高了 4.6 倍。高脂血症大鼠中 SLN 的 PD 研究显示血脂谱下降 36 小时，而悬浮液则显示 24 小时。 (C) 2016 Elsevier B.V. 保留所有权利。
The intent of this investigation was to improve pharmacokinetic (PK) and pharmacodynamic (PD) effects of Rosuvastatin calcium (RC) by solid lipid nanoparticles (SLNs). RC is anti-hyperlipidemic drug with low oral bioavailability (20%) due to first-pass metabolism. Hot homogenization followed by ultrasonication method was used to prepare RC-SLNs with stearic acid, glyceryl behenate and glyceryl trilaurate as lipid matrices, egg lecithin and poloxamer 188 as surfactants. The prepared SLNs were tested for particle size, PDI, zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro release. Further, PLC and PD studies were conducted on selected SLNs. No changes in physical stability of the optimized SLN were observed at refrigerated and room temperature for 90 days. SLNs prepared with glyceryl trilaurate having average size of 67.21 +/- 1.71 nm, PDI of 0.25 +/- 0.01, ZP of -28.93 +/- 0.84 mV with 93.51 +/- 0.34% EE was considered as optimized. DSC and XRD studies revealed that no interaction occurred between the drug and lipid. SEM and TEM studies revealed that SLNs were nearly spherical in shape. PK studies showed improvement in the oral bioavailability (extent of absorption) of SLNs by 4.6-fold when compared to that of suspension. PD study of SLNs in hyperlipidemic rats exhibited a decrease in lipid profile for 36 h, while a suspension exhibited for 24 h. (C) 2016 Elsevier B.V. All rights reserved.