Construction Of Argatroban-modified-membrane Filter And The Detection Of It’s Surface Characteristics

Background:Blood purification therapy has been widely used in the treatment of many critical illness, the process will inevitably involve cardiopulmonary bypass. However, due to pipeline, dialyzer / filter and other artificial materials can not be completely bio-compatible, so the activation of coagulation factors can not be avoided. Therefore, improving the biocompatibility of artificial materials, especially the blood compatibility, has became a hot spot in today’s materials science, engineering, medicine. From cellulose membranes to synthetic membranes, the blood compatibility of the dialysis membranes was improved greatly. But it still need a little systemic anticoagulant. Vascular endothelial cells with best blood compatibility, and antithrombotic agents secreted by the cells also play an important role in preventing blood to form thrombosis. So, simulating the endothelial cells, improving the blood compatibility, loading and releasing the anticoagulant on membrane surface, may improve the effectiveness and cut down the dosage as well.Objective:We will construct a new filter membrane of excellent blood compatiblity and with anticoagulant drug loaded by electrostatic molecular self-assembly technique. The new type of membrane can release anticoagulant locally onto the interface of membrane contacting with blood flow.Methods:In order to get modified filter, Chitosan - Argatroban mixed solution and the hyaluronic acid solution will rush through the polysulfone membrane filter in turns,according to the principle of electrostatic molecular self-assembly technique.( 1) To confirm every step of the molecular self-assemble coatings, we use scanning electron microscopy to observe the surface morphology and thickness of the filter membrane. (2) To observe the changes of membrane hydrophilicity, we use contact angle measuring machine to measure the hydrophilicity angle of the membrane surface. (3) Explore the conditions of measuring argatroban concentration required for high-performance liquidchromatography. Then we do a sustained-release test, using high-performance liquid chromatography to measure the argatroban concentration of slow-release liquid, in order to get the drug release characteristics of membrane.Results:1 electron microscope shows that: in the molecular self-assembly process, the membrane surface morphology gradually changes,from non-uniform distribution of island-shaped granule to dense granule which is evenly distributed. After four pairs of molecular layers, thickness show a gradually increase .2 Hydrophilicity angle shows: two different hydrophilic surfaces appear alternately; and bimolecular layers with an increase in its hydrophilic angle which continuously becomes smaller.3 The results of drug release: argatroban has been successfully loaded,but the concentration is very low.Conclusions:1 electrostatic self-assembly of chitosan/(hyaluronic acid) can modify the surface of polysulfone membrane, and significantly improve its hydrophilicity. To avoid affecting the dialysis performance of the membrane, four pairs of molecular layers are most suitable.2 Argatroban can be loaded by chitosan/hyaluronic acid electrostatic self-assembly.,and argatroban can be slowly released.