冰片阿司匹林固体脂质纳米粒的制备及脑靶向分布

Preparation and brain targeting distribution of borneol aspirin solid lipid nanoparticles

制备冰片(Borneol,BO)-阿司匹林(Asprin,ASP)固体脂质纳米粒(ASP-BO solid lipid nanoparticles,AB-SLN),探讨BO对ASP脑靶向分布的影响。采用微乳-低温固化法制备AB-SLN;采用扫描电镜、透射电镜和激光粒度仪对其药学性质进行表征,以ASP的含量为指标进行稳定性考察;通过小鼠体内药动学实验,考察BO对ASP在脑组织中分布的影响。结果表明,AB-SLN在电镜下呈均匀的圆球状结构,其粒径为(195±12)nm,表面Zeta电位为(-32±2.7)mV;AB-SLN对药物BO-ASP[m(BO)∶m(ASP)=3∶1]的包封率为(76±5.2)%,室温放置14 d后包封率为0 d时的98.4%,稳定性较好。m(BO)∶m(ASP)=1∶1、3∶1、5∶1时,ASP在小鼠脑组织中的脑药浓度分别为未加冰片组(A-SLN)的1.94、2.55与2.71倍,药峰时间(t_(m))较A-SLN组提前1 h,且AB-SLN组ASP血药浓度始终低于A-SLN组,表明BO能够促进ASP向小鼠脑组织中分布实现脑靶向作用。可为ASP在脑部疾病治疗领域提供一种脑靶向制剂而具有广阔的临床应用前景。

The research aimed to prepare the borneol(BO)-aspirin(ASP)solid lipid nanoparticles(AB-SLN)and investigate the effect of BO on the brain targeted distribution of ASP.Microemulsion low temperature curing method was used to prepare the AB-SLN,and the pharmaceutical properties of AB-SLN were characterized by SEM and TEM.The stability of AB-SLN was investigated by the ASP content using as the evaluation index.The effects of BO on the brain targeted distribution of ASP were also investigated by pharmacokinetic experiments of AB-SLN in mice.The results showed that the structure of AB-SLN was uniform spherical shape,its particle size was(195±12)nm and surface Zeta potential was(-32±2.7)mV;The encapsulation rate of AB-SLN for BO-ASP[m(BO)∶m(ASP)=3∶1]was(76±5.2)%,after stored at room temperature for 14 days,the encapsulation rate was 98.4%of that at 0 day,this indicated that the AB-SLN had a better stability for ASP.When m(BO)∶m(ASP)=1∶1,3∶1,5∶1,the brain drug concentration of ASP in mouse brain tissue was 1.94,2.55 and 2.71 times of that in A-SLN group,and the peak time(t_(m)=1 h)was earlier than that of A-SLN group.Although the blood concentration of ASP in AB-SLN and A-SLN groups showed a phenomenon from low to high with the administration time,the blood concentration of ASP of AB-SLN was always lower than that of A-SLN,this indicated that BO could promote the distribution of ASP to mouse brain tissue.The combination of ASP and BO to produce AB-SLN can provide a brain targeting agent of ASP for the treatment of brain diseases and has a broad clinical application prospect.