Study On The Colon Enzyme Specific Degraded Amphiphilic Copolymer

The physiology functional characters of gastrointestinal systems comprises to the barriers that bioactive macromolecules can't achieve their bioavailability. Those macromolecule drugs needing enter into the blood circulation to exert therapy effect, insulin as an example, have to traverse two kinds of biologic barriers:One is the hydrophilic fixed water layer in intestinal epithelium; the other is the hydrophobic liposome layer of epithelium cell.A novel enzyme responsive amphiphilic copolymer was synthesized. The copolymer was composed of hydrophobic polylactide (PLA) and hydrophilic methyl poly (ethyl glycol) (MPEG) block. The two blocks were conjugated through 5,5'-azodisalylic acid (OLZ) (MPEG-OLZ-PLA). The chemical structure of the copolymer was verified by FTIR, NMR and GPC. The GPC and 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-PLA self-assembled into spherical micelles and the diameter increased with the molecule weight of MPEG increasing. The change of CMC of different copolymers was opposite to that of the diameter.The enzyme-degradation experiment demonstrated that the MPEG-OLZ-PLA micelles could be specifically degraded in rat cecum contents. And the degradation curve of MPEG₂₀₀₀-OLZ-PLA₅₀₀₀ had two platforms 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. While the degradation curve of MPEG₅₀₀₀-OLZ-PLA₅₀₀₀ was a little different, the second platform of which was very short because of the longer hydrophilic segment. Such degradation behavior of the copolymers suggested of potential usefulness to colon-site specific delivery.