Background: Carbamazepine (Cbz) is the first-line drug for epileptic seizures but exhibits fluctuation at the plasma level and side effects after oral administration.To overcome these problems, Cbz should be targeted directly into the brain. Therefore, the current experimental design was aimed to formulate and optimize the Cbz containing solid lipid nanoparticles (SLNs) for brain delivery via intranasal administration to get rid of oral complications associated with Cbz. Methods: A full factorial design was performed to evaluate the effect of variables (X1 lipid concentration, X2 surfactant concentration, and X3 sonication time) on the response variables (size of nanoparticles, entrapment efficiency, and drug release). A two-level, three-factor design was employed herewith, and eight formulations were developed. Further, the formation of Cbz containing SLNs was characterized by compatibility, particle size, entrapment efficiency, and drug release with the support of Fourier Transform Infra-Red (FTIR), Zeta sizer, Transmission Electron Microscopy (TEM), Ultra-violet (U.V.), and High-Performance Liquid Chromatography (HPLC). Results: All eight formulations were characterized through particle size, entrapment efficiency, and invitro drug release performance. Out of eight characterized formulations, SN1 showed the most promising results, including particle size of 210 ± 2.14 nm, entrapment efficiency of 42.1 ± 1.09%, and drug release of 61.3 ± 2.02% and considered an optimized batch. Additionally, the optimized batch SN1was further evaluated for an in-vivo study on male Wistar Rats. Conclusion: The study revealed that a high amount of drug was reached into the brain through intranasal administration compared to the intravenous route. Therefore, it can minimize the unwanted side effects of the Cbz associated with oral administration. The formulation SN1 possesses an excellent drug targeting efficiency of 3.014. Finally, the current experimental work concluded that there is a direct pathway from the intranasal route to the brain. This delivery system can be beneficial for directly delivering CNS-active drugs into the brain.

中文翻译：

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通过卡马西平负载固体脂质纳米颗粒的鼻内给药增强脑递送：优化、药代动力学分析、体外和体内药物释放研究

背景：卡马西平（Cbz）是治疗癫痫发作的一线药物，但口服给药后存在血浆水平波动和副作用。为了克服这些问题，Cbz 应该直接靶向大脑。因此，当前的实验设计旨在配制和优化含有 Cbz 的固体脂质纳米颗粒 (SLN)，用于通过鼻内给药进行脑递送，以消除与 Cbz 相关的口腔并发症。方法：进行全因子设计以评估变量（X1 脂质浓度、X2 表面活性剂浓度和 X3 超声处理时间）对响应变量（纳米粒子大小、包封效率和药物释放）的影响。为此采用了两水平、三因素设计，并开发了八种配方。更远，在傅里叶变换红外 (FTIR)、Zeta 粒度分析仪、透射电子显微镜 (TEM)、紫外 (UV) 的支持下，通过相容性、粒径、包封效率和药物释放来表征含有 SLN 的 Cbz 的形成，和高效液相色谱法 (HPLC)。结果：通过粒径、包封效率和体外药物释放性能对所有八种制剂进行了表征。在八种表征制剂中，SN1 显示出最有希望的结果，包括 210 ± 2.14 nm 的粒径、42.1 ± 1.09% 的包封效率和 61.3 ± 2.02% 的药物释放，被认为是优化批次。此外，针对雄性 Wistar 大鼠的体内研究，进一步评估了优化的批次 SN1。结论：该研究表明，与静脉内给药相比，鼻内给药可使大量药物进入大脑。因此，它可以最大限度地减少 Cbz 与口服给药相关的不良副作用。制剂SN1具有3.014的优异药物靶向效率。最后，目前的实验工作得出结论，从鼻内途径到大脑有一条直接途径。这种输送系统有利于将中枢神经系统活性药物直接输送到大脑中。目前的实验工作得出结论，从鼻内途径到大脑有一条直接途径。这种输送系统有利于将中枢神经系统活性药物直接输送到大脑中。目前的实验工作得出结论，从鼻内途径到大脑有一条直接途径。这种输送系统有利于将中枢神经系统活性药物直接输送到大脑中。