The objective of this study was to develop an in-situ gel containing lorazepam (LZM) loaded nanostructured lipid carriers (NLCs) for direct nose-to-brain delivery in order to increase drug therapeutic efficacy in the treatment of epilepsy. Accordingly, LZM loaded NLCs were formulated using emulsification solvent diffusion and evaporation method; then the effects of the formulation variables on different physicochemical characteristics of NLCs were investigated. Thermosensitive in-situ gels containing LZM-NLCs were prepared using a combination of chitosan and β-glycerol phosphate (β-GP). The anticonvulsant efficacy of LZM-NLCs-Gel was then examined using the pentylenetetrazole (PTZ) model. The optimised NLCs were spherical, showing the particle size of 71.70 ± 5.16 nm and the zeta potential of -20.06 ± 2.70 mV. The pH and gelation time for the chitosan solution with 15% (w/v) β-GP were determined to be 7.12 ± 0.03 and 5.33 ± 0.58 min, respectively. The in-vivo findings showed that compared with the control group and the group that received LZM-Gel, the occurrence of PTZ-induced seizures in the rats was significantly reduced by LZM-NLCs-Gel after intranasal administration. These results, therefore, suggested that the LZM-NLCs-Gel system could have potential applications for brain targeting through nasal route and might increase LZM therapeutic efficacy in the treatment of epilepsy.

中文翻译：

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含有劳拉西泮 NLC 的壳聚糖基热敏凝胶用于治疗癫痫持续状态的体外和体内评价。

本研究的目的是开发一种含有劳拉西泮 (LZM) 负载的纳米结构脂质载体 (NLC) 的原位凝胶，用于直接从鼻到脑递送，以提高药物治疗癫痫的疗效。因此，负载 LZM 的 NLC 采用乳化溶剂扩散和蒸发法配制；然后研究了配方变量对 NLC 不同理化特性的影响。使用壳聚糖和 β-甘油磷酸 (β-GP) 的组合制备含有 LZM-NLC 的热敏原位凝胶。然后使用戊四唑 (PTZ) 模型检查 LZM-NLCs-Gel 的抗惊厥功效。优化后的 NLC 呈球形，粒径为 71.70 ± 5.16 nm，zeta 电位为 -20.06 ± 2.70 mV。含有 15% (w/v) β-GP 的壳聚糖溶液的 pH 值和胶凝时间分别确定为 7.12 ± 0.03 和 5.33 ± 0.58 分钟。体内研究结果表明，与对照组和LZM-Gel组相比，LZM-NLCs-Gel鼻内给药后大鼠PTZ诱发癫痫发作的发生率显着降低。因此，这些结果表明，LZM-NLCs-Gel 系统可能具有通过鼻途径进行脑靶向的潜在应用，并可能提高 LZM 在癫痫治疗中的治疗效果。LZM-NLCs-Gel 鼻内给药后可显着减少大鼠 PTZ 诱发的癫痫发作。因此，这些结果表明，LZM-NLCs-Gel 系统可能具有通过鼻途径进行脑靶向的潜在应用，并可能提高 LZM 在癫痫治疗中的治疗效果。LZM-NLCs-Gel 鼻内给药后可显着减少大鼠 PTZ 诱发的癫痫发作。因此，这些结果表明，LZM-NLCs-Gel 系统可能具有通过鼻途径进行脑靶向的潜在应用，并可能提高 LZM 在癫痫治疗中的治疗效果。