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抗精神分裂症药物纳米脂质体通过鼻腔途径直接且增强地递送至大脑。

Direct and enhanced delivery of nanoliposomes of anti schizophrenic agent to the brain through nasal route.

作者信息

Upadhyay Pratik, Trivedi Jatin, Pundarikakshudu Kilambi, Sheth Navin

机构信息

Department of Pharmaceutical Technology, L. J. Institute of Pharmacy, Ahmedabad, Gujarat, India.

Department of Pharmaceutical Sciences, Saurashtra University, Rajkot, Gujarat, India.

出版信息

Saudi Pharm J. 2017 Mar;25(3):346-358. doi: 10.1016/j.jsps.2016.07.003. Epub 2016 Aug 5.

Abstract

The problem of inadequate oral bioavailability of Quetiapine Fumarate, a lipophilic drug used for schizophrenia, due to hepatic metabolism and repulsion by brain barrier was attempted in this study. Combination of two approaches, viz. Quetiapine inclusion into the liposomal carrier for better diffusion and administration through nasal route to avoid hepatic metabolism and barrier elimination was applied. Thin film hydration followed by sonication method was employed in liposome preparation and the formulation was optimized using 3 full factorial design. The number of sonication cycles () of 2 min and 80% amplitude and molar ratio of constructional components such as cholesterol to egg phosphatidylcholine () as independent variables and a % of entrapment efficiency () and cumulative drug release () at 6 h as dependent variables was selected. Batch F7 prepared by 2 cycles of sonication and 1:3 M ratio of cholesterol:egg phosphatidylcholine was optimized as a consequence of substantial entrapment efficiency of 75.63 ± 3.77%, and 99.92 ± 1.88% drug release and 32.33 ± 1.53% drug diffusion, which was optimum among all other batches at 6 h. Diffusion study was done for all the batches of liposomal formulation by using sheep nasal mucosa and good amount with better diffusion rate was measured which proved liposomal dispersion a virtuous delivery system for brain drug delivery through nasal route. Results of , ciliotoxicity and gamma scintigraphy studies on mice supported the above inference.

摘要

富马酸喹硫平是一种用于治疗精神分裂症的亲脂性药物,由于肝脏代谢和血脑屏障的排斥作用,其口服生物利用度不足的问题在本研究中得到了探讨。采用了两种方法的组合,即:将喹硫平包封于脂质体载体中以实现更好的扩散,并通过鼻腔途径给药以避免肝脏代谢和屏障清除。脂质体制备采用薄膜水化后超声处理的方法,并使用三因素全因子设计对制剂进行优化。选择2分钟、80%振幅的超声处理循环次数()以及胆固醇与蛋黄卵磷脂等结构成分的摩尔比()作为自变量,6小时时的包封率()和药物累积释放率()作为因变量。由于包封率高达75.63±3.77%,药物释放率为99.92±1.88%,药物扩散率为32.33±1.53%,在6小时时优于所有其他批次,因此由2次超声处理循环和胆固醇与蛋黄卵磷脂1:3摩尔比制备的F7批次被优化。通过绵羊鼻黏膜对所有批次的脂质体制剂进行了扩散研究,测量到了具有较好扩散速率的良好量,这证明脂质体分散体是通过鼻腔途径进行脑内药物递送的良好递送系统。对小鼠进行的、纤毛毒性和γ闪烁扫描研究结果支持了上述推断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e054/5357100/301bf4bbc00e/gr1.jpg

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