Elmowafy Mohammed, Ibrahim Hany M, Ahmed Mohammed A, Shalaby Khaled, Salama Ayman, Hefesha Hossam
a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt.
b Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
Drug Deliv. 2017 Nov;24(1):932-941. doi: 10.1080/10717544.2017.1337823.
Atorvastatin (AT) is a widely used lipid-regulating drug to reduce cholesterol and triglycerides. Its poor aqueous solubility and hepatic metabolism require development of drug delivery systems able to improve its solubility and bypass hepatic effect. For this purpose, atorvastatin nanostructured lipid carriers (AT-NLCs) were prepared and characterized. AT-NLCs were prepared by emulsification using high-speed homogenization followed by ultrasonication. The prepared NLCs showed particle size between 162.5 ± 12 and 865.55 ± 28 nm while zeta potential values varied between -34 ± 0.29 and -23 ± 0.36 mV. They also showed high encapsulation efficiency (>87%) and amorphous state of the drug in lipid matrix. Pharmacokinetic parameters of optimized formulation (NLC-1; composed of 2% Gelucire 43/01, 8% Capryol PGMC, 2% PluronicF68 and 0.5% lecithin) revealed 3.6- and 2.1-fold increase in bioavailability as compared to atorvastatin suspension and commercial product (Lipitor), respectively. Administration of NLC-1 led to significant reduction (p < .05) in the rats' serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and significant increase in high-density lipoprotein (HDL). This improvement was confirmed histologically by minimizing the associated hepatic steatosis. These investigations demonstrated the superiority of NLCs for improvement of oral bioavailability and in vivo performance of AT.
阿托伐他汀（AT）是一种广泛使用的调脂药物，用于降低胆固醇和甘油三酯。其水溶性差和肝脏代谢的特点要求开发能够提高其溶解度并绕过肝脏作用的药物递送系统。为此，制备并表征了阿托伐他汀纳米结构脂质载体（AT-NLCs）。AT-NLCs通过高速均质乳化后超声处理制备。制备的NLCs粒径在162.5±12至865.55±28nm之间，而ζ电位值在-34±0.29至-23±0.36mV之间。它们还显示出高包封率（>87%）以及药物在脂质基质中的无定形状态。优化制剂（NLC-1；由2%的Gelucire 43/01、8%的Capryol PGMC、2%的PluronicF68和0.5%的卵磷脂组成）的药代动力学参数显示，与阿托伐他汀混悬液和市售产品（立普妥）相比，生物利用度分别提高了3.6倍和2.1倍。给予NLC-1导致大鼠血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）水平显著降低（p<0.05），高密度脂蛋白（HDL）显著升高。通过将相关的肝脏脂肪变性降至最低，组织学证实了这种改善。这些研究证明了NLCs在改善AT的口服生物利用度和体内性能方面的优越性。
