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Construction of Multifunctional Coatings for Cardiovascular Devices via Layer-By-Layer Self-Assembly of Hyperbranched Polyethers

Author: HuXiaoFen
Tutor: ShenJiaZuo；JiJian
School: Zhejiang University
Course: Polymer Chemistry and Physics
Keywords: Static electricity Covalent bond Layer-by-layer assembly Hyperbranched polyether Heparin polymer A partial controlled release carrier Endothelialization
CLC: R318.08
Type: PhD thesis
Year: 2010
Downloads: 159
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Abstract


The multi-functional film coating to achieve the anti-coagulation, endothelial cells induced and local controlled drug release is an important means to solve the problem of clinical application of cardiovascular implant materials. In this paper molecular terminal with a large number of hydroxyl groups in hyperbranched polyether for the study of the main body, the layers of assembly, multifunctional thin-film coating material is prepared, using electrostatic and covalent bonding through the modification and activation of the functional group on the end of the hyperbranched polyether to explore the feasibility of cardiovascular implant surface coating applied. A heparan hyperbranched polyether electrostatic layer assembly build a multi-functional film coating materials research first terminal functional groups of hyperbranched poly (3 - ethyl-3 - (hydroxymethyl) epoxybutane) (HBPO) sulfonic acid group-modified, hydrophobic HBPO converted to a water-soluble heparin hyperbranched and polyether HBPO-SO 3 . By fluorescence probe method, particle size analysis, and transmission electron microscopy (TEM) to characterize the polymer self-assembly behavior in aqueous solution, that when HBPO-SO 3 concentration above the critical micelle concentration ( CMC) 0.017 mg / mL, it can spontaneously assemble to form a size between 25 to 70 nm, the kernel is hydrophobic hyperbranched polyether chain, the outer layer is a negatively charged sulfonic groups spherical micelles. The results further show that the fluorescent probe method HBPO-SO 3 single the dispersed macromolecules state and its self-assembled aggregates are entrapped the object small molecule hydrophobic hydrophobic environment. Recalcification clotting time measurement result proved that the heparin-like nature, the molecular ends of a sulfonic acid group of the modified hyperbranched polyether makes HBPO-SO 3 and reflects the good antithrombogenicity; vitro activity Determination and cell morphology proved HBPO-SO 3 with low cytotoxicity and good biocompatibility, suitable for direct contact with the blood in vivo environment. Hyperbranched polyether of the sulfonic acid-modified, not only improved the biocompatibility of the polymer, while the molecular ends of a large number of sulfonic acid groups so that the polymer has the nature of a strong polyelectrolyte. HBPO-SO 3 as heparin substitutes alternately assembled with polycationic chitosan electrostatic layer multilayer film was prepared. The data indicate that an atomic force microscope (AFM), HBPO-SO 3 Loading multilayer film Self-assembled form of aggregates, the hydrophobic region of the large number of nano-size is formed in the multilayer film. Multilayers by \The fluorescence spectra and UV spectra of the results show that, compared with the pre-package containing Act pyrene load a multilayer film prepared by the diffusion method, having a higher packet load and a better controlled release capabilities. By the same manner of loading of the diffusion method, in the multilayer film package containing the hydrophobic drug has anti-restenotic function a probucol compared with heparin / chitosan multilayers HBPO-SO 3 < / sub> / chitosan multilayers due to the hydrophobic region having a nanometer size, on the diffusion of organic solvent is not limited, and can be successfully achieved package upload and controlled release of probucol. Recalcification clotting time of the determination results show that even antibacterial chitosan as the outermost layer, the surface of the multilayer film also has a good antithrombogenicity. HBPO-SO 3 / chitosan multilayer film is expected to become a multifunctional coating materials with antibacterial, anticoagulant and local controlled release of hydrophobic drugs ability. Two reactive the hyperbranched polyether covalently layers assembled to construct multifunctional film coating material of study further advantage of the multi-terminal hydroxyl groups of the hyperbranched polyether HBPO prepared the end of the chemical reaction activity with an amino compound having a nitro group benzene ester group hyperbranched polyether HBPO-NO 2 . The aminated surface of the substrate, HBPO-NO 2 and PEI layers of self-assembly process by a covalent bond, formation of a multilayer film having a covalently crosslinked structure stable. HBPO-NO 2 / PEI multilayers compatible hydrophobic hyperbranched polyether with cationic polyelectrolyte two different properties of substances, and therefore has a unique package load performance. The multilayer film may be provided by the action of the protonated package containing anionic model drugs Ponceau 2R, adjusting the drug loading solution pH can affect Ponceau 2R in the multilayer film package loading and release, at neutral pH value under the conditions of multilayers can achieve high drug loading and controlled release. The multilayer film can be used as the template situ preparation of nano-silver particles, the amount of nano silver loading increases with increasing the PEI number of layers in the multilayer film. Multilayer films can also be successfully entrapped hydrophobic drug probucol, and to achieve long-term release. Endothelial cells cultured in vitro results show HBPO-NO 2 / PEI multilayer film having a the impedance cell adhesion, as the film thickness increases, this effect becomes more obvious. (The HBPO NO 2 / PEI) n / HBPO-NO 2 multilayers surface graft bioactive molecules collagen and peptides REDV, promote adhesion to endothelial cells, to improve the compatibility of the multilayer film surface cells. In particular, collagen function (HBPO-NO 2 / PEI) 5 / HBPO-NO 2 multilayers exhibit significantly promote endothelial cell adhesion capacity. Therefore, the chemical reaction the activity HBPO-NO 2 / PEI multilayers not only a variety of therapeutic agents can be used as local controlled release carrier, and modified by the surface of the biological function of the regulation of cell behavior has As the value of the cardiovascular implants multifunctional coating on the surface of potential applications.

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CLC: > Medicine, health > Basic Medical > Medical science in general > Biomedical Engineering > General issues > Biomaterial
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