Electroformatiom Of Lipid Assembly And Magnetic Controllable Drug Release

All important functions of the cell are related to the biological membrane, and the studies of biological membrane have become the important contents and the research direction in biology. The lipid bilayer structure is the versatile model to study many features of biological membrane, such as lareral fluidity, curvature, phase separation, membrane protein recombination, osmotic stress on membrane, and so on. It is a promising research of the preparation, and the drug release appliation of the nanomaterials based on the lipid assembly carrier. But the lipid assembly induced by electric field needs to be further explorated, and the effect of the magnetic heat and magnetic oscillation on drug release is still not very clear. In this thesis, the coplanar interdigitated microelectrodes with different sizes were firistly prepared by using photolithography and electrochemistry technology. Secondly, the formation of lipid vesicle and lipid tube using interdigitated microelectrodes in AC electric field was investigated in detail. Lastly combining magnetic nanoparticles, two types of magnetic loading drug lipid vesicles were fabricated. Drug release induced by AC magnetic field(AMF) was investigated both experimentally and theoretically.The coplanar interdigitated microelectrodes with width from 50~200μm were prepared by using photolithography and electrochemistry technology. The parameters of exposure time, ultrasonic time and corrosion time were optimized to be 2s,7s and 40 s, respectively. The thickness of prepared microelectrodes is 160 nm and thoughness of microelectrodes was as same as that of bare ITO surface by AFM measurement.The formation of lipid vesicle and lipid tube using interdigitated microelectrodes in AC electric field was investigated in detail with various parameters. Both lipid vesicles and lipid tubes can be formed with different lipid species(DOPC, egg PC, DPPC,etal), electrode width(50~200μm), solution height(1~2mm), amplitude(1~10V) and frequency(1~10k Hz) of AC fields. A phase diagram of egg PC vesicle formation based on varying the AC frequency and amplitude was obtained experimentally, which can be used to select the electric field for desired size vesicle preparation. The length of formed lipid tube is about 200 μm, and the stability of these tubes is great. Combining our experimental results and the simulation data using Comsol, we proposed that the lateral electric field component(Ex) was the main driving force of nanotube growth. The key control factor of lipid vesicles or lipid tube formation was analysized by combining experimental data with simulations.A well-known method of coprecipitation was used to synthsize and characterize the citrate-coated and APTES-coated magnetic nanoparticles respectively. Two types of magnetic lipid vesicles were fabricated, i.e., lipid vesicles with negatively charged MNPs inside and lipid vesicles with positively charged MNPs on their surfaces. The results of the carboxyfluorescein(CF) and chemotherapy drug doxorubicin(Dox) release induced by AC magnetic field(AMF) indicate that these releases synchronize with the AC magnetic field switch very well. Release percentage increases with increasing frequency in the system of magnetic loading drug vesicles with MNPs inside, while it increases firstly and then decreases with increasing frequency in the system of magnetic loading drug vesicles with MNPs on the surfaces with the maximum release at 2 k Hz. The magnetic heating effect dominates the release of magnetic loading drug vesicles with MNPs inside, while both magnetic heating and oscillation effects play important roles on the release of magnetic loading drug vesicles with MNPs on the surfaces. These two type magnetic lipid vesicles exhibit different drug releases mechanisms on the base of the similation and experimental results. The in vitro cytotoxicity experiments of Dox loaded vesicles toward He La cells were further performed, which show these magnetic responsive drug carries have obvious effect on cell dying triggered by external non-invasively AMF.It demonstrates that coplanar interdigitated microelectrodes break the tradition way of producing lipid vesicles with two opposite electrodes. A new electrode system was created to realize the phospholipid vesicle preparation. A new simple and flexible method of lipid tube preparation was also founded. The key control factor of lipid vesicles or lipid tube formation in coplanar interdigitated microelectrodes was obtained by combining experimental data with simulations. It provides a theoretical basis for controlled assembly of phospholipids assembly in AC electric field. The results of controlled drug release behavior of these formed magnetic carriers triggered by magnetic field and their influence on cell death in vitro provide an important guidance to design and prepare the high efficient, controllable, intelligent targeted-drug carriers, which also shows the potential application in the clinical treatment of cancer.