E Eleraky Nermin, M Omar Mahmoud, A Mahmoud Hemat, A Abou-Taleb Heba
Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Deraya University, Minia 61768, Egypt.
Pharmaceutics. 2020 May 14;12(5):451. doi: 10.3390/pharmaceutics12050451.
The opposing effect of the blood-brain barrier against the delivery of most drugs warrants the need for an efficient brain targeted drug delivery system for the successful management of neurological disorders. Temazepam-loaded nanostructured lipid carriers (NLCs) have shown possibilities for enhancing bioavailability and brain targeting affinity after oral administration. This study aimed to investigate these properties for insomnia treatment. Temazepam-NLCs were prepared by the solvent injection method and optimized using a 4 full factorial design. The optimum formulation (NLC-1) consisted of; Compritol 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer 407 (0.3 g), with an entrapment efficiency of 75.2 ± 0.1%. The average size, zeta potential, and polydispersity index were determined to be 306.6 ± 49.6 nm, -10.2 ± 0.3 mV, and 0.09 ± 0.10, respectively. Moreover, an in vitro release study showed that the optimized temazepam NLC-1 formulation had a sustained release profile. Scintigraphy images showed evident improvement in brain uptake for the oral Tc-temazepam NLC-1 formulation versus the Tc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of Tc-temazepam NLC-1 formulation (292.7%), compared to that of oral Tc-temazepam suspension. Besides, the NLC formulation exhibited a distinct targeting affinity to rat brain. In conclusion, our results indicate that the developed temazepam NLC formulation can be considered as a potential nanocarrier for brain-mediated drug delivery in the out-patient management of insomnia.
血脑屏障对大多数药物递送具有阻碍作用，因此需要一种高效的脑靶向给药系统，以成功治疗神经系统疾病。载有替马西泮的纳米结构脂质载体（NLCs）在口服给药后显示出提高生物利用度和脑靶向亲和力的可能性。本研究旨在探究这些特性用于治疗失眠。采用溶剂注射法制备替马西泮-NLCs，并使用4因素全因子设计进行优化。最佳配方（NLC-1）由Compritol 888 ATO（75毫克）、油酸（25毫克）和泊洛沙姆407（0.3克）组成，包封率为75.2±0.1%。平均粒径、zeta电位和多分散指数分别测定为306.6±49.6纳米、-10.2±0.3毫伏和0.09±0.10。此外，体外释放研究表明，优化后的替马西泮NLC-1配方具有缓释特性。闪烁扫描图像显示，口服Tc-替马西泮NLC-1配方相对于Tc-替马西泮混悬液的脑摄取有明显改善。药代动力学数据显示，与口服Tc-替马西泮混悬液相比，Tc-替马西泮NLC-1配方的相对生物利用度显著提高（292.7%）。此外，NLC配方对大鼠脑表现出明显的靶向亲和力。总之，我们的结果表明，所开发的替马西泮NLC配方可被视为在门诊治疗失眠中用于脑介导药物递送的潜在纳米载体。
