胰岛素pH敏感接枝共聚物囊泡的制备

发布时间：2019-05-28 15:11

【摘要】：目的利用酰化反应合成维生素E-琥珀酰聚赖氨酸接枝共聚物(N-tocopheryl-N'-succinyl-ε-polylysine,TOS-SA-PLL)作为载体材料,胰岛素作为模型药物,制备p H敏感接枝共聚物囊泡。方法采用核磁共振扫描和红外光谱对接枝共聚物TOS-SA-PLL结构进行表征;利用2,4,6-三硝基苯磺酸法对接枝共聚物的取代度进行测定;利用动态光散射法对囊泡的粒径,多分散性和Zeta电位进行测定;采用超滤离心法测定囊泡的包封率和载药量以及载药囊泡在不同p H条件下的体外释药行为。结果接枝共聚物自组装形成的囊泡平均粒径为165.7~232.3 nm,Zeta电位为-32.2~-20.1 m V;载胰岛素共聚物囊泡的包封率最高可达70.15%,载药量(w)为6.55%;体外释放结果表明该接枝共聚物囊泡的释放行为具有p H敏感性的特征。结论 TOS-SA-PLL接枝共聚物囊泡具有p H敏感的特点,其作为水溶性生物大分子药物的载体,在胃肠道传递领域具有较好的应用前景。
[Abstract]:Objective To synthesize vitamin E-succinyl-N '-succinyl-1-polylysine (TOS-SA-PLL) as carrier material and to prepare p-H-sensitive graft copolymer vesicles. Methods The structure of the graft copolymer TOS-SA-PLL was characterized by nuclear magnetic resonance scanning and infrared spectroscopy. The degree of substitution of the graft copolymer was determined by means of 2,4,6-trinitrobenzene sulfonic acid. The particle size, polydispersivity and Zeta potential of the vesicle were determined by dynamic light scattering method. The encapsulation rate and the drug-carrying amount of the vesicles and the in vitro release behavior of the drug-loaded vesicles under different p-H conditions were determined by ultrafiltration. Results The average particle size of the vesicle formed by the self-assembly of the graft copolymer was 165.7-232.3 nm, the Zeta potential was-32.2--20.1 m V, the encapsulation rate of the carrier-loaded copolymer vesicle was up to 70.15%, and the drug-carrying amount (w) was 6.55%. In vitro release results show that the release behavior of the graft copolymer vesicles has a characteristic of p-H sensitivity. Conclusion The TOS-SA-PLL graft copolymer vesicle has the characteristics of p-H sensitivity, which is a carrier of the water-soluble biological macromolecular drug, and has a good application prospect in the field of gastrointestinal transmission.
【作者单位】：沈阳药科大学药学院;沈阳药科大学生命科学与生物制药学院;
【基金】：国家自然科学基金资助项目(31170967)
【分类号】：R943

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