Preparation And Sustained Release Performance Of Nanoparticle-embedded Polyelectrolyte Multilayer Membrane

This thesis gives an overview of application of layer by layer self-assembly technology(LBL)in the field of biomedical materials in the past twenty-five years and a survey of the commonly-used materials.The applications in of LBL technology in 2-dimensional and 3-dimensional multilayer membrane materials in the field of drug-controlled release are also introduced.In the study,functionalized multilayer membranes have been developed:Firstly,a series of poly(MATMAC-St)nanogels with core-shell structure were prepared via a dispersion copolymerization by using[2-(Methacryloyloxy)ethyl]trimethylammonium chloride(MATMAC)and styrene(St)as monomers in the water-ethanol mixture media.The impact of the ratios of the two monomers,M ATM AC and St,and the ratios of water and ethanol on the sizes of the nanogels were investigated.The core-shell structure of Poly(MATMAC-St)gels were characterized by transmission electron microscopy(TEM).The results showed that the ratio of the monomers had a significant impact on the particle size while the ratio of ethanol and water presented the effect on the nanogel stability.The nanogel size was decreased with pH increase or salt concentration,and surface potential was decreased with the decrease of pH or salt concentration.Positively-charged nanogel-contained multilayer membranes were constructed by alternative assembly through electrostatic interaction between the poly(MATMAC-St)nanogels as positively constructive unit and poly(styrene sulfonate)(PSS)as negatively constructive unit,and then an cover layer of(PDDA-OH/PSS)2.5(PDDA-OH/AA/PDDA-g-SA/PSS)5 was introduced on the top layer of the formed membrane to slow the drug release.The effect of the assembly behaviors of the nanogels and PS S as well as the cover layers on the formation and structure of multilayer membrane,drug loading capacity and drug release performance were then investigated.The result showed that the concentration of nanogel in the membrane got the benefit of the stronger charge of the nanogel and the higher salt concentration of assembly solution.Meanwhile,uniform membrane could be formed via the assembly PS S and nanogels which were synthesized using different ratio of monomers and under different ratio of ethanol and water in the medium.The nanogel concentration in the multilayered films was increase with the number of the assembled nanogel layers.The naonogel-containing membranes showed the notable drug loading capacities which were improved with the assembly number of nanogels and a degreased pH of assembly solution,and drug release behavior demonstrated more sustained manner with the introduction of the cover layers.Mesoporous silica particles were synthesized through the hydrolysis of tetraethyl orthosilicate by using hexadecyl trimethyl ammonium bromide(CTAB)as templet.Mesoporous silica-embedded multilayer films were built via alternative assembly of mesoporous silica nanoparticles(MSN)as negatively constructive unit and Poly(dimethyl-diallylammonium-chloride)(PDDA)as positively constructive unit.Gentamicin(GM)can be incorporated into the formed films due to the nanoporous structure and the negative charge in the mesoporous silica.The property of MSN,the assembly performance and the drug release behavior were studied.BET results showed the MSN had a specific surface area up to 980 m2/g.TEM images presented MSN a mesoporous structure.It was observed by XRD that the crystal structure of MSN was hexahedron.The thickness of the multilayer films was increased with the number of the assembly layer.The MSN-embedded films demonstrated a notable drug loading property and a more sustained releasing property with the introduction of the cover layer.Finally,nanoparticle-embedded polyelectrolyte multilayer membrane was prepared with Mesoporous silica particles,nanogels,PDDA and PSS.Oppositely charged drugs were loaded into the multilayer films based on electrostatic interactions between the drugs and the nanoparticles.The nanoparticle-embedded films showed a notable drug loading property with different drugs and a sustained releasing property with the introduction of the cover layer.The developed nanoparticle-embedded polyelectrolyte multilayer membrane demonstrate excellent performance,the abilities to simultaneously incorporate different drugs and the drug release property in a sustained manner.Meanwhile,post-drug loading manner is able to avoid the deactivation of bioactive drug molecules during the LBL procedure.Therefore,the developed coating approach may have great potential to be applied in medical devices and/or clinic medical treatment.