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目的:合成三分枝低聚乙二醇(TEG)为亲水部分和分别以6个碳(R1),8个碳(R2),12个碳(R3)的脂肪链为疏水部分的3种两亲性分子(TEG-R1,TEG-R2,TEG-R3),并对其作为难溶性药物载体进行研究。方法:通过苯磺酰化、取代反应、还原反应、酯化后形成酰胺成功合成3个化合物,通过核磁进行结构表征,应用芘荧光探针法进行临界胶束浓度的测定,透射电镜观察其自组装形态。自组装溶剂蒸发法制备载药鬼臼毒素胶束,对载药胶束进行粒径表征,并考察3种两亲性分子的溶血性。结果:核磁证明3种两亲性分子均成功合成,TEG-R1,TEG-R2,TEG-R3的临界胶束浓度分别为50,50,10mg·L-1。电镜观察呈20～50nm的类球形状态。3种两亲性分子均能制备成载药胶束且粒径分布在100～200nm。溶血性实验证明接枝6碳脂肪链的两亲性分子中TEG-R1不会引起溶血。结论:3种两亲性分子在水溶液中均具有胶束化行为,且均能作为难溶性药物载体;其中TEG-R1不会引起溶血有望成为新型的药物载体。
OBJECTIVE: To synthesize three kinds of oligomeric ethylene glycol (TEG) with hydrophilic part and six kinds of aliphatic chains with 6 carbons (R1), 8 carbons (R2) and 12 carbons (R3) Amphipathic molecules (TEG-R1, TEG-R2, TEG-R3) and investigated their use as poorly soluble drug carriers. Methods: Three compounds were successfully synthesized by benzenesulfonylation, substitution reaction, reduction reaction and esterification to form amides. The structures of the compounds were characterized by NMR. The critical micelle concentration was determined by pyrene fluorescence probe method. The transmission electron microscopy Assembly form. Preparation of drug-loaded podophyllotoxin micelles by self-assembly solvent evaporation method, particle size characterization of drug-loaded micelles, and investigate the hemolytic properties of three amphipathic molecules. Results: Three kinds of amphiphilic molecules were successfully synthesized by NMR. The critical micelle concentrations of TEG-R1, TEG-R2 and TEG-R3 were 50, 50 and 10 mg · L-1, respectively. Electron microscopy showed a spherical state of 20 ~ 50nm. All three kinds of amphiphilic molecules can be prepared into drug-loaded micelles with particle size distribution in the range of 100 ~ 200 nm. Hemolytic experiments demonstrated that TEG-R1 did not cause hemolysis in amphiphilic molecules grafted with 6-carbon fatty chains. CONCLUSION: All three amphiphilic molecules have the properties of micellarization in aqueous solution, and both of them can be used as poorly soluble drug carriers. Among them, TEG-R1 does not cause hemolysis and is expected to become a novel drug carrier.