Nanotechnology Laboratory, Department of Pharmaceutics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh, India 506009.
AAPS PharmSciTech. 2011 Mar;12(1):422-30. doi: 10.1208/s12249-011-9604-3. Epub 2011 Mar 1.
The aim of our present work was to develop indinavir O/W submicron lipid emulsions (SLEs) loaded with lipoamino acids for specific delivery to brain. Tetradecyl aspartic acid (A) and decyl glutamic acid (G) loaded stable SLEs of indinavir having a mean size range of 210-220 nm and average zeta potential of -23.54±1.2 mV were developed using homogenization and ultrasonication. The cumulative % drug release from different SLEs varied in between 26% and 85%. The formulations, SLE, SLE-A3, and SLE-G3 were stable to the centrifugal stress, dilution stress, and storage at RT. The total drug content and entrapment efficiency were determined by HPLC method. During pharmacokinetic studies in male Wistar rats there was no significant difference in the serum levels of indinavir for SLE, SLE-A3 and SLE-G3 formulations at all time points. In tissue distribution studies, the therapeutic availability (TA) of indinavir in brain and kidneys for SLE-A3 were 4.27- and 2.66-fold whereas for SLE-G3 were 2.94 and 2.12 times, respectively, higher than that of indinavir solution. But when compared with that of SLE, in brain tissue the levels of indinavir from SLE-G3 and SLE-A3 varied in between 2.5- and 3.38-fold. While in case of the kidney, it was between 1.23- and 1.54-fold only. However, the TA is not significantly different in tissues like the heart, liver, and spleen. Thus, brain-specific delivery of indinavir was improved by including tetradecyl aspartic acid and decyl glutamic acid in submicron lipid emulsions.
本研究旨在开发载脂蛋白载药的辛那瓦林 O/W 亚微米脂乳（SLE），用于脑内靶向递药。采用匀质法和超声法制备了平均粒径范围在 210-220nm 之间、平均 Zeta 电位为-23.54±1.2mV 的载辛那瓦林的十四酰天冬氨酸（A）和癸酰谷氨酸（G）负载的稳定 SLE。不同 SLE 的累积药物释放百分比在 26%到 85%之间变化。SLE、SLE-A3 和 SLE-G3 制剂在离心力、稀释力和室温下储存均稳定。总药物含量和包封效率通过 HPLC 法测定。在雄性 Wistar 大鼠的药代动力学研究中，SLE、SLE-A3 和 SLE-G3 制剂在所有时间点的血清辛那瓦林水平均无显著差异。在组织分布研究中，SLE-A3 中辛那瓦林在脑和肾脏中的治疗利用率（TA）分别为辛那瓦林溶液的 4.27-和 2.66 倍，而 SLE-G3 分别为 2.94-和 2.12 倍。但与 SLE 相比，SLE-G3 和 SLE-A3 中的辛那瓦林在脑组织中的水平在 2.5-3.38 倍之间变化。而在肾脏中，仅为 1.23-1.54 倍。然而，在心脏、肝脏和脾脏等组织中，TA 没有显著差异。因此，通过将十四酰天冬氨酸和癸酰谷氨酸包含在亚微米脂乳中，提高了辛那瓦林的脑内靶向递药。
