结肠酶特异响应性两亲高分子载体的合成和表征

SYNTHESIS AND CHARACTERIZATION OF A ENZYME SPECIFIC DEGRADED AMPHIPHILIC COPOLYMER

合成了一种可在结肠部位被特异酶解的两亲性嵌段高分子,由聚丙交酯(PLA)疏水嵌段和聚乙二醇(PEG)亲水嵌段组成,两者通过5,5′-偶氮二水杨酸(OLZ)偶联,其中的偶氮键可被结肠部位的偶氮还原酶特异酶解.利用FTIR、NMR和GPC等方法表征了共聚物的结构,并通过透射电镜(TEM)和动态光散射(DLS)等方法研究了该高分子载体在水溶液中的组装行为.结果表明MPEG-OLZ-b-PLA可在水介质中形成尺寸在30nm左右的球形胶束,并在大鼠全盲肠提取液中被特异性酶解。

A novel enzyme responsive amphiphilic copolymer was synthesized.The copolymer was composed of hydrophobic polylactide（PLA） and hydrophilic α-methoxy-poly（ethyl glycol）（MPEG） block.The two blocks were conjugated through 5,5＇-azodisalylic acid（OLZ）（MPEG-OLZ-b-PLA）.The chemical structure of the copolymer was verified by FTIR,NMR and GPC.The NMR characterization demonstrated that the copolymers could be synthesized by esterification and purified by precipitation and dialysis.The micellization behavior of the copolymer in aqueous media was studied with transmission electron microscopy（TEM） and dynamic light scattering（DLS）.The results showed that MPEG-OLZ-b-PLA self-assembled into spherical micelles with diameter at about 30 nm.The critical micelle concentration（CMC） of the copolymer was 2.69 × 10^-3 g/L.The enzyme-degradation experiment demonstrated that the MPEG-OLZ-b-PLA micelles could be specifically degraded in rat cecum contents.And the degradation curve had two time platform with no change in azo content.The first platform phase resulted from the induction period of the enzyme so that desirable concentration of the enzyme could be achieved for initialing the degradation of the copolymers.The second could be attributed to the slow dynamic process for azoreductase to migrate into the micelles.Such degradation behavior of the copolymers suggested of potential usefulness to colon-site specific delivery.