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 42 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 99mTc-temazepam NLC-1 formulation versus the 99mTc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of 99mTc-temazepam NLC-1 formulation (292.7%), compared to that of oral 99mTc-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.

中文翻译：

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纳米结构脂质载体介导替马西m的脑部输送：设计和体内研究。

血脑屏障对大多数药物的输送具有相反的作用，因此需要一个有效的脑靶向药物输送系统来成功治疗神经系统疾病。口服替马西m的纳米结构脂质载体（NLC）已显示出增强口服后生物利用度和脑靶向亲和力的可能性。这项研究旨在调查失眠治疗的这些特性。通过溶剂注入法制备替马西m NLC，并使用42个全因子设计对其进行优化。最佳配方（NLC-1）包括：888 ATO（75 mg），油酸（25 mg）和Poloxamer®407（​​0.3 g），包封率为75.2±0.1％。测得的平均尺寸，ζ电势和多分散指数分别为306.6±49.6 nm，-10.2±0.3 mV和0.09±0.10，分别。此外，一项体外释放研究表明，优化的替马西m NLC-1制剂具有持续释放特性。闪烁扫描图像显示，与99mTc-替马西m混悬液相比，口服99mTc-替马西m NLC-1制剂的大脑摄取有明显改善。药代动力学数据表明，与口服99mTc-替马西m混悬液相比，99mTc-替马西m NLC-1制剂的相对生物利用度显着提高（292.7％）。此外，NLC制剂对大鼠脑显示出独特的靶向亲和力。总之，我们的结果表明，开发的替马西m NLC制剂可被视为在失眠的门诊治疗中脑介导的药物输送的潜在纳米载体。一项体外释放研究表明，优化的替马西N NLC-1制剂具有持续释放特性。闪烁显像图像显示，与99mTc-替马西suspension混悬液相比，口服99mTc-替马西m NLC-1制剂的大脑摄取有明显改善。药代动力学数据表明，与口服99mTc-替马西m混悬液相比，99mTc-替马西m NLC-1制剂的相对生物利用度显着提高（292.7％）。此外，NLC制剂对大鼠脑显示出独特的靶向亲和力。总之，我们的结果表明，开发的替马西m NLC制剂可被视为在失眠的门诊治疗中脑介导的药物输送的潜在纳米载体。一项体外释放研究表明，优化的替马西N NLC-1制剂具有持续释放特性。闪烁显像图像显示，与99mTc-替马西suspension混悬液相比，口服99mTc-替马西m NLC-1制剂的大脑摄取有明显改善。药代动力学数据表明，与口服99mTc-替马西m混悬液相比，99mTc-替马西m NLC-1制剂的相对生物利用度显着提高（292.7％）。此外，NLC制剂对大鼠脑显示出独特的靶向亲和力。总之，我们的结果表明，开发的替马西m NLC制剂可被视为在失眠的门诊治疗中脑介导的药物输送的潜在纳米载体。闪烁显像图像显示，与99mTc-替马西suspension混悬液相比，口服99mTc-替马西m NLC-1制剂的大脑摄取有明显改善。药代动力学数据表明，与口服99mTc-替马西m混悬液相比，99mTc-替马西m NLC-1制剂的相对生物利用度显着提高（292.7％）。此外，NLC制剂对大鼠脑显示出独特的靶向亲和力。总之，我们的结果表明，开发的替马西m NLC制剂可被视为在失眠的门诊治疗中脑介导的药物输送的潜在纳米载体。闪烁显像图像显示，与99mTc-替马西suspension混悬液相比，口服99mTc-替马西m NLC-1制剂的大脑摄取有明显改善。药代动力学数据表明，与口服99mTc-替马西m混悬液相比，99mTc-替马西m NLC-1制剂的相对生物利用度显着提高（292.7％）。此外，NLC制剂对大鼠脑显示出独特的靶向亲和力。总之，我们的结果表明，开发的替马西m NLC制剂可被视为在失眠的门诊治疗中脑介导的药物输送的潜在纳米载体。此外，NLC制剂对大鼠脑显示出独特的靶向亲和力。总之，我们的结果表明，开发的替马西m NLC制剂可被视为在失眠的门诊治疗中脑介导的药物输送的潜在纳米载体。此外，NLC制剂对大鼠脑显示出独特的靶向亲和力。总之，我们的结果表明，开发的替马西m NLC制剂可被视为在失眠的门诊治疗中脑介导的药物输送的潜在纳米载体。