Construction Of Complex Oral Colon-specific Drug Delivery System Of Dependence Of PH And Enzymes

In recent years, Oral Colon-specific Drug Delivery System(OCDDS) has attracted a greatdeal of interest, because it can reduce the release of oral medications in the stomach and smallintestine, make them release specifically in the colon, improve the drug concentration ofcolonic pathological changes and reduce the dosage of drugs.In this study,the complex OCDDS of dependence of pH and enzymes was constructedby the graft copolymerization and the crosslinking and balling technology based ondextran(Dex) as the matrix. First of all, the graft polymer Dex-g-PSSS was obtained throughPloy (Sodium4-styrene sulfonate)(PSSS) grafted on dextran by using cerium salt-hydroxylgroup redox initiation system. The microspheres C(Dex-g-PSSS) were synthesized byinverse crosslinking-emulsion method with epichlorohydrin as the crosslinking agent.Thechemical structure and physicochemical characters of C(Dex-g-PSSS) microspheres wererepresented by infrared spectroscopy (FTIR), optical microscope and Zeta potential analyzer.And the swelling ratio of C(Dex-g-PSSS) was investigated in different pH solution. Theexperimental results show that the microspheres C(Dex-g-PSSS) had been synthesized by thegraft copolymerization and the crosslinking and balling technology, the Dex-g-PSSS ofPSSS grafting degree of11.86g/100g was obtained under the condition of reactiontemperature of50oC; reaction time of6h; initiator concentration of0.87mol/L; cerium saltconcentration of1.2x10-2mol/L and acid concentration of0.08mol/L.Then, the adsorption property and the release behavior of the microspheresC(Dex-g-PSSS) for5-fluorouracil (5-FU) were investigated. The experimental results showthat in the medium with pH2, the cross-linked microspheres C(Dex-g-PSSS) exhibit a strongadsorption ability for5-FU because of strong electrostatic interactions and have an adsorptioncapacity of154mg/g, displaying high drug-carrying efficiency. The in vitro release behavior of the drug-carrying microspheres is highly dependent on pH and dextranase. In simulatedgastric fluids(pH1), they release a little, whereas in simulated colonic fluids(PBS with pH7.4in the presence of dextranase), a sudden delivery phenomenon of the drug will occur,displaying an excellent colon-specific drug delivery behavior. At the same time， theadsorption property and the release behavior of the microspheres C(Dex-g-PSSS) forTinidazole (TNZ) were examined, also displaying an excellent colon-specific drug deliverybehavior. Therefore, the microspheres C(Dex-g-PSSS) is an complex OCDDS of dependenceof pH and enzymes.