Preparation and characterization of intestinal transporter-targeted polymeric micelles  

靶向小肠转运体的聚合物胶束的制备与表征（英文）

作　　者：Chuyu He Yao Jin Yunqiang Deng Yang Zou Shidi Han Chuhang Zhou Yuanhang Zhou Xinru Li Yanxia Zhou Yan Liu 何楚瑜;靳尧;邓运强;邹洋;韩诗迪;周楚杭;周远航;李馨儒;周艳霞;刘艳(北京大学医学部药学院分子药剂学与新释药系统北京市重点实验室,北京100191)

机构地区：Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems,School of Pharmaceutical Sciences Peking University Health Science Center,Beijing 100191,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2018年第7期490-497,共8页中国药学（英文版）

基　　金：The National Natural Science Foundation of China(Grant No.81673366);the National Key Science Research Program of China(973 Program,Grant No.2015CB932100)

摘　　要：The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelles targeting to the organic cation transporter 2（OCTN2） were constructed by combining carnitine conjugated poly（2-ethyl-2-oxazoline）-poly（D,L-lactide）（Car-PEOz-PLA） with monomethoxy poly（ethylene glycol）-poly（D,L-lactide）（mP EG-PLA）. The structure of the synthesized Car-PEOz-PLA was confirmed by -1H NMR, TLC and ammonium reineckate precipitation reaction, and the number-average molecular weight determined by GPC was 7260 g/mol with a low PDI of 1.44. Coumarin 6-loaded carnitine modified polymeric micelles prepared by film hydration method were characterized to have a nano-scaled size of about 31 nm in diameter, uniform spherical morphology, high drug loading content of 0.098%±0.03% and encapsulation efficiency of 92.67%±2.80%. Moreover, the carnitine-modified micelles exhibited the similar in vitro release behavior in SGF and SIF, and evidently enhanced intestinal absorption of poorly water-soluble agent. Therefore, the designed OCTN2-targeted micelles might have a promising potential for oral delivery of poorly water-soluble drugs.小肠上皮是难溶性药物口服递送的主要屏障,本研究基于小肠上皮表达的新型有机阳离子转运体2(OCTN2),设计并制备了由肉毒碱修饰的聚(2-乙基-2-噁唑啉)-聚乳酸(Car-PEOz-PLA)与聚乙二醇-聚乳酸(mPEG-PLA)构成的聚合物胶束。用~1H NMR、TLC、硫氰酸铬铵(雷氏盐)沉淀法确证了所合成的Car-PEOz-PLA的结构,用GPC测定其分子量为7260 g/mol,PDI=1.44。采用薄膜水化法制备包载香豆素6的肉毒碱修饰的聚合物胶束,其粒径约为31 nm,载药量和包封率分别为0.098%±0.03%和92.67%±2.80%。其在模拟胃液和肠液中具有相似的体外释放行为,并明显增强了难溶药物的小肠吸收。因此,靶向OCTN2的聚合物胶束在口服递送难溶药物方面具有潜在的优势。

关 键 词：CARNITINE Organic cation transporter 2 （OCTN2） Polymeric micelles In vitro release Intestinal absorption 

分 类 号：R943[医药卫生—药剂学]