Department of Pharmaceutical Technology, National Research Centre, Cairo, Egypt; Department of Pharmaceutics and Pharmaceutical Technology, Future University in Egypt, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Eur J Pharm Sci. 2018 Mar 30;115:77-87. doi: 10.1016/j.ejps.2018.01.028. Epub 2018 Jan 16.
Management of epilepsy requires brain delivery therapy, therefore, this study was aimed to prepare lamotrigine loaded poly-ɛ-(d,l-lactide-co-caprolactone) (PLCL) nanoparticles using spontaneous emulsification solvent diffusion method. Nanoparticles for brain delivery required to have a particle size <200 nm, polydispesity index <0.2 and a sustained drug release properties. For such aim different factors were considered in preparing the nanoparticles as PLCL monomers' ratio, type of organic solvent used to prepare the nanoparticles, amount of PLCL and Pluronic®F127 in the nanoparticles. Prepared nanoparticles were characterized for their shape, particle size, polydispersity index, zeta potential, encapsulation efficiency, drug loading capacity, process yield and in-vitro drug release pattern. The in-vivo investigation for brain delivery of selected nanoparticles delivered by intravenous route was investigated in rats and compared to that for oral tablet. The obtained nanoparticles were spherical in shape. The amount of surfactant and PLCL affected the properties of the obtained nanoparticles. Using a mixture of organic solvent in preparing the nanoparticles improved its properties. The nanoparticles prepared using PLCL with monomers' ratio of 25:75, had particle size value of 125 nm, polydispersity index value of 0.184, zeta potential value of -39 mV and encapsulation efficiency value of 99%, was selected to study their efficacy to deliver the drug to the brain. The tested nanoparticles showed higher values of T, C, AUC, and MRT in homogenized rat brain, compared to oral lamotrigine tablet, while the bioavailability of the oral tablet was higher in rat plasma compared to that for the nanoparticles. This reflects that brain was the main distribution site for tested nanoparticles, and plasma was the main distribution site for oral tablets. This confirms the goal of the selected formulation as brain delivery nanoparticles.
癫痫的治疗需要脑部递药疗法，因此，本研究旨在使用自发乳化溶剂扩散法制备载拉莫三嗪的聚-（ε-己内酯-co-己内酯）（PLCL）纳米粒。脑部递药用纳米粒需要粒径<200nm、多分散指数<0.2 且具有持续药物释放特性。为此，在制备纳米粒时考虑了不同因素，如 PLCL 单体的比例、用于制备纳米粒的有机溶剂的类型、纳米粒中 PLCL 和 Pluronic®F127 的用量。所制备的纳米粒的形状、粒径、多分散指数、Zeta 电位、包封效率、载药量、收率和体外药物释放模式均进行了表征。通过静脉途径给予选定的纳米粒的体内脑部递药研究在大鼠中进行，并与口服片剂进行了比较。所得纳米粒呈球形。表面活性剂和 PLCL 的用量影响所得纳米粒的性质。使用混合有机溶剂制备纳米粒可改善其性质。采用单体比例为 25:75 的 PLCL 制备的纳米粒，粒径为 125nm，多分散指数为 0.184，Zeta 电位为-39mV，包封效率为 99%，被选择来研究其将药物递送至脑部的效果。与口服拉莫三嗪片剂相比，测试的纳米粒在匀浆大鼠脑内显示出更高的 T、C、AUC 和 MRT 值，而口服片剂在大鼠血浆中的生物利用度高于纳米粒。这表明测试的纳米粒主要分布在脑内，而口服片剂主要分布在血浆中。这证实了所选制剂作为脑部递药纳米粒的目标。
