基于聚乙二醇双硬脂酸酯的注射用载多西他赛液晶纳米粒的研制  

Preparation of PEG Distearate-based Liquid Crystalline Nanoparticles Loaded with Docetaxel for Injection

作　　者：王熙临 许欣媛 陈黎明 潘颋 翁伟宇 WANG Xilin;XU Xinyuan;CHEN Liming;PAN Ting;WENG Weiyu(Shanghai Key Lab.of New Drug Design,School of Pharmacy,East China University of Science and Technology,Shanghai 200237)

机构地区：[1]华东理工大学药学院,上海市新药设计重点实验室,上海200237

出　　处：《中国医药工业杂志》2023年第12期1731-1737,1744,共8页Chinese Journal of Pharmaceuticals

摘　　要：本研究旨在考察将聚乙二醇双硬脂酸酯作为液晶材料制备载药液晶纳米粒(LCNPs)的可行性。分别合成了2种液晶材料,甲氧基聚乙二醇(m PEG)双硬脂酸酯(m PEG350-DS)和聚乙二醇(PEG)双硬脂酸酯(S-PEG400-S)。所得的2种材料遇水均可形成溶致液晶,其中S-PEG400-S液晶可被稳定地分散而得到LCNPs。以多西他赛为模型药,添加适量卵磷脂后可获得具有良好负载能力的LCNPs,其粒径为137.9 nm、ζ电位为–19.7 m V、包封率96.5%、载药量为3.4%、含量为标示量(2 mg/m L)的98.2%。载药LCNPs在体外抑瘤试验和体内药动学研究中显示出优于市售注射液(泰索帝)的抑瘤效果和显著的长循环特征。根据偏光显微镜、小角X射线散射和冷冻透射电镜的观察结果,推测该LCNPs中的液晶相态为海绵(L3)相。上述试验结果表明,S-PEG400-S具备成为载药LCNPs材料的良好潜力。The aim of this study was to investigate the feasibility of using polyethylene glycol(PEG)distearate as liquid crystalline(LC)materials to prepare drug-loaded LC nanoparticles(LCNPs).Two LC materials,mPEG distearate(mPEG350-DS)and PEG distearate(S-PEG400-S),were respectively synthesized.Both obtained derivatives could form lyotropic LC in water,and the LC of S-PEG400-S could be stably dispersed to prepare LCNPs.With docetaxel as the model drug,the LCNPs with good drug-loading capacity were obtained by adding appropriate amount of lecithin into the formula.The particle size,ζpotential,encapsulation efficiency,loading capacity,and content of the docetaxel-loaded LCNPs were 137.9 nm,–19.7 mV,96.5%,3.4%,and 98.2%of the labeled amount(namely 2 mg/mL),respectively.The docetaxel-loaded LCNPs showed better antitumor effects and remarkably longer blood circulation time than the commercially available injection(TaxotereⓇ)in in vitro antitumor experiment and in vivo pharmacokinetic study.The LC phase in the LCNPs was inferred to be sponge(L3)phase according to the observations of polarizing microscopy,small angle X-ray scattering and cryo-transmission electron microscopy.In conclusion,the S-PEG400-S showed a good prospect for LCNPs-based drug delivery system.

关 键 词：聚乙二醇衍生物 硬脂酸酯 液晶纳米粒 海绵相 多西他赛 注射剂 药物动力学 

分 类 号：R944.9[医药卫生—药剂学]