Construction Of Biocompatible And Drug Delivery Mutilayers Films Via Electrostatic Self-Assembly

Electrostatic self-assembly was explored to develop multilayer film coating with anti-coagulation, anti-bactreial and drug delivery properties.Construction of Anticoagulant biomolecular Multilayer Films via Electrostatic Self-assembly Technique — The electrostatic self-assembly method was used to design and modify the interventional therapeutic material surface. The albumin bioinert multilayer and heparin bioactive multilayer film coatings were designed with electrostatic layer-by-layer (LBL) supramolecular assembly method for the anticaogulant, respectively.The positive charge was induced onto biomedical 316Lstainless steel surface by adsorption of a layer of cationic polyethylenimine (PEI). The positive charged 316Lstainless steel sheet was alternatively dipped into bovine serum albumin (1mg/mL) and PEI (1mg/mL) PBS solutions to construct multilayer film. The process of electrostatic self-assembly of PEI/albumin was monitored by ¹²⁵I radio labeled method, electrochemical impendence spectroscopy (EIS). The atomic force microscopy (AFM) results indicated the densely albumin coating on biomedical 316Lstainless steel could be gained with simple control the number of assembly. The EIS data revealed that the multilayer coating was stable in tris-HCI (pH 7.35) buffer solution for 21 days. The ¹²⁵I radio labeled method indicated that less than 10% albumin was eluted by PBS in 40days. The static platelet adhesion indicated that the PEI/albumin deposited stainless steel could resist the platelet adhesion effectively.The LBL self-assembly of heparin and PEI was used to construct bioactive anti-coaulation multilayer coating. The contact angle and electrochemical impendence spectroscopy (EIS) were used to monitor that layer-by-layer assembled process. The reflection absorption spectra (RAS) and x-ray photoelectron spectroscopy (XPS) data confirmed that heparin molecule was successfully immobilized onto 316Lstainless steel. The EIS data and contact angle test revealed that the PEI/heparin multilayer films were stable in tris-HCI (pH 7.35) buffer solution for 21 days. The static plateletadhesion and static clotting time experiments indicated that the heparin terminated PEI/heparin multilayer films deposited stainless steel could resist the platelet adhesion and prolong the static clotting time effectively. Such an easy processing and shape-independent method may have good potential for the construction anticoagulant surface of cardiovascular devices.Construction of collaborated anticoagulant and anti-bacterial multilayer film via Electrostatic Self-assembly Technique—The anti-bacterial chitosan and anticoagulant heparin were explored to construct collaborated anticoagulant and anti-bacterial multilayer film. Layer-by-layer assembled chitosan and heparin at different pH were monitored by Quartz Crystal Microbalance (QCM). The wettability, dye binding ability of the chitosan terminated heparin/chitosan multilayer films varied with environment pH was investigated by contact angle measurements and UV observation. The results indicated when the heparin/chitosan multilayer film prepared at low pH contacted with related high environment pH, the chitosan occurred to deionization. The dionization of chitosan led to some excess free unpaired anionic group, which paired with ionized amino group of chitosan molecular at prepared conditions. The excess free unpaired anionic group would penetrate onto the chitosan layer with that the interpenetration of chitosan and heparin layers. The penetration of free anionic group resulted in that the chitosan terminated film showed some heparin performance and presented collaborated chitosan and heparin performance. The collaborated surface property of chitosan/heparin multilayer film was controlled by the degree of deionization of chitosan and the interepentration between chitosan and heparin molecules. The lower assembly pH led to stronger interepentration and had higher deionization of chitosan/heparin film at physiological environment (pH 7.4). These led to the chitosan terminated chitosan/heparin multilayer film present stronger heparin performance. The dye adsorption test indicated that the free anionic group in deionized chitosan/heparin multilayer film could adsorb a large amout of cation and showed pH-dependent loading. In vitro anticoagulant and anti-bacterial tests indicated the deionized chitosan/heparin clearly showed collaborated anti-bacterial and anticoagulant properties. Thecollaborated anticoagulant and anti-bacterial of chitosan/heparin multilayer film with drug loading capabilities may have good potential for fabrication of biomedical device coating.Construction of Drug Delivery Multilayer Film Coatings via Chitosan Deionization—According to the revelation of deionization effect on chitosan/heparin multilayer film drug loading, In this section, a common strong polyanion (poly (sodium 4-styrenesulfonate) (PSS)) was used to assemble multilayer film with chitosan at pH 2.0:2.0 for detailed study of the deionization of chitosan effect on model drug loading and releasing behavior.The contact angle and UV-vis sepecrroscopy testes indicated that the PSS/chitosan multilayer film prepared at pH 2.0:2.0 could come into being free sulfate group when the multilayer film contacted with high environment pH and resulted in deioniztion of chitosan. The free sulfate group could be used to improve cationic drug loading. The salts of loading solution shielded the electrostatic interaction of polyelectrolyte and multilayer film swollen, hence controlled the dye loading.The buffered solution greatly increased dye release from multilayer films due to swelling. The loading pH and salt concentration had significant effects on the degree of the dye penetrating into bulk films and the methylene blue release. The controlled loading capabilities and release behavior of PSS/chitosan multilayer films by the deionization of weak polyelectrolyte demonstrated here may be useful toward drug delivery applications.Construction of Drug Delivery Coatings via Exponential Growth Multilayer Film— PEI/alginate multilayer films were studied to develop a novel exponential growth multilayer film and assess the possibility to develop drug delivery coatings. The QCM was used to monitor the assembly process, which indicated that the PEI/alginate multilayer film assembly had exponential growth behavior. The exponential growth PEI/alginate multilayer films could greatly improved the loading amount ofnegatively charged model drug Crocein Orange G in a few layers. The release study indicated that the exponential growth PEI/alginate multilayer film not only largely improved the loading amount of model drug, but also greatly prolonged the model drug release time. The multilayer film was crosslinked with CaCl2 or heating treatment, which could further prolong the model drug release time. The multilayer film with exponential growth could improve the amount of drug loading in limited layers, which perhaps break down the limitation of classical electrostatic self-assembly on drug loading and presented an inspiration for design of long-term drug release coating.