Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India 576104.
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India 576104; Alkem Laboratories Ltd., Mumbai, India.
Life Sci. 2016 Oct 15;163:38-45. doi: 10.1016/j.lfs.2016.08.033. Epub 2016 Sep 1.
The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain. The formulations were evaluated for vesicle size, zeta potential, and entrapment efficiency. The morphology was studied by Transmission Electron Microscopy (TEM). In vivo efficacy was assessed by performing pharmacokinetic study in Wistar albino rats following intranasal administration of the formulations in comparison to intravenous bolus administration of pure drug. The mean vesicle size of optimized liposomes ranged from 90 to 100nm with low polydispersity index (<0.5). The entrapment efficiency of optimized liposomes was between 50 and 60%, functionalized liposomes showed maximum entrapment. The TEM images showed predominantly spherical vesicles with smooth bilayered surface. All formulations showed prolonged diffusion controlled drug release. The in vivo results showed that liposomal formulations provided enhanced brain exposure. Among the formulations studied, PEGylated liposomes (LP-16) had shown greater uptake of risperidone into the brain than plasma. High brain targeting efficiency index for LP-16 indicating preferential transport of the drug to brain. The study demonstrated successful formulation of surface modified risperidone liposomes for nasal delivery with brain targeting potential.
本研究旨在通过鼻腔途径开发用于脑靶向的功能性利培酮脂质体，以实现精神分裂症的有效治疗管理。利培酮脂质体采用薄膜水化法制备。通过使用 Design-Expert（®）软件优化各种参数，如脂质比率和脂质与药物比率，以获得高包封率和最小的囊泡尺寸。通过包覆硬脂胺和 MPEG-DSPE 对优化后的脂质体进行表面修饰，以增强向大脑的穿透能力。对制剂进行了囊泡大小、Zeta 电位和包封效率的评估。通过透射电子显微镜（TEM）研究了形态。通过在 Wistar 白化大鼠中进行药代动力学研究，评估了制剂的体内功效，将其与静脉推注给予纯药物进行比较。优化后的脂质体的平均囊泡大小范围为 90 至 100nm，具有低多分散指数（<0.5）。优化后的脂质体的包封效率在 50%至 60%之间，功能化脂质体显示出最大的包封效率。TEM 图像显示主要为球形囊泡，具有光滑的双层表面。所有制剂均显示出延长的扩散控制药物释放。体内结果表明，脂质体制剂提供了增强的大脑暴露。在所研究的制剂中，PEG 化脂质体（LP-16）显示出比血浆更高的利培酮进入大脑的摄取量。LP-16 的高脑靶向效率指数表明药物优先向大脑转运。该研究成功地对具有脑靶向潜力的利培酮表面修饰脂质体进行了鼻腔给药的制剂开发。
