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口服给药是患者顺应性最好的给药方式,而小肠上皮是口服药物吸收的主要屏障.为了克服小肠上皮屏障口服递送难溶性药物,本研究设计合成了小肠胆酸转运体的底物脱氧胆酸偶联的聚(2-乙基-2-噁唑啉)-聚(D,L-乳酸)(DA-PEOz-PLA),并基于小肠胆酸特殊的转运途径构建了由DA-PEOz-PLA和mPEG-PLA组成的聚合物胶束以包载模型药物香豆素6(C6).用核磁共振氢谱和薄层色谱对DA-PEOz-PLA的结构进行了确证,用凝胶渗透色谱测得其分子量为10 034(PDI = 1.51).载C6的聚合物胶束的粒径和PDI分别为40.11 nm和0.212,载药量为0.085％.透射电镜观察胶束呈现较规则的球形.另外,与未修饰胶束相比,去氧胆酸修饰的聚合物胶束能进一步增强胶束的跨膜转运效率.跨膜转运机制的研究结果表明去氧胆酸的修饰丰富了胶束的跨膜转运途径.因此,所制备的去氧胆酸修饰的聚合物胶束在难溶性药物的口服递送方面具有潜在的优势.“,”Oral administration is the best way for the most patients due to the good compliance,and intestinal epithelium is the main barrier of oral drug absorption.In order to overcome the small intestine epithelial barrier to orally deliver water-insoluble drugs,deoxycholic acid(DA),a substrate of the intestinal bile acid transporters,conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)(DA-PEOz-PLA)was designed and synthesized,and deoxycholic acid-modified polymeric micelles composed of DA-PEOz-PLA and mPEG-PLA were fabricated to encapsulate model drug coumarin 6(C6)based on intestinal bile acid pathway.The structure of DA-PEOz-PLA was confirmed using 1H NMR and TLC,and the molecular weight measured by GPC was 10 034 g/mol with a PDI of 1.51.The C6-loaded polymeric micelles with drug loading content of 0.085％were characterized to have 40.11 nm in diameter and uniform spherical morphology observed by TEM.Furthermore,the deoxycholic acid-modified polymeric micelles were demonstrated to further enhance the transmembrane transport efficiency.The mechanic study evidenced that anchorage of deoxycholic acid onto the micelles surface enriched their transcellular transport pathway.Therefore,the designed deoxycholic acid-modified polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs.