Study On Preparation,characterization And Biological Properties Of Three Kinds Of Silica Nanomaterials

With the development of materials technology,more and more biomaterials are used in the Smart response Drug Delivery System?DDS?,so as to improve the targeting and water solubility of drugs,reduce the toxic and side effects of drugs,improve the therapeutic effect of drugs,and ultimately reduce the pain of patients.The key to the design of DDS is the choice of carrier materials.With the widespread application of nanotechnology in the field of medicine,it has been found that nanocarrier-mediated DDS?NDDS?has the advantages of increasing cell uptake,prolonging drug circulation time,enhancing system stability,and promoting the accumulation of drugs in lesions site.An ideal NDDS would retain the drug in the nanocarrier particles until it reaches the lesion site,and release the loaded drug only when exposed to a release signal,which can minimize the toxic and side effects of the drug and bring an unprecedented dawn to improve the curative effect of the treatment of critically ill drugs.In this paper,nano silica?nSiO₂?,mesoporous silica?MSNs?and its composites mesoporous silica/chitosan?MSNs/CS?were studied.Field emission electron microscopy?FE-SEM?,transmission electron microscopy?TEM?,thermogravimetry?TGA?,X-ray diffraction?XRD?,Fourier transform infrared spectroscopy?FT-IR?,nanoparticle size/Zeta potential analyzer and N₂ adsorption/desorption were used to characterize the materials.The effects of reaction conditions on the dispersibility,particle size and particle size distribution of the materials were analyzed,and the optimal preparation process conditions was discussed.Drug delivery experiments and a series of biocompatibility experiments also were carried out,with a view to providing reference for MSNs and MSNs/CS in the field of intelligent response NDDS and biomedical applications.The main research and results are as follows:?1?In this paper,nSiO₂ was prepared by using the ultrasonic-assisted Stober method,using Si?OC₂H₅?₄ as the raw material and NH₃·H₂O as the catalyst.The effects of ultrasonic power,ultrasonic time and magnetic stirring speed on the morphology and dispersion of nSiO₂ were investigated.The experimental results showed that the nSiO₂ with a good monodispersity of about 600 nm was successfully prepared when the ultrasonic power,ultrasonic time and magnetic stirring speed were 160 W,5 min and 999 rpm respectively.The yield of ultrasonic cavitation was measured by iodine release method,and the mechanism of its preparation of nSiO₂ was discussed.Compared with the traditional Stober method,Ultrasonic assisted Stober method has the advantages of time saving,energy saving and simple operation,which is expected to become a new nano material preparation technology.?2?MSNs were successfully synthesized by the sol-gel assisted hard template method using Si?OC₂H₅?₄ as raw material,CTAB as template,NH₃·H₂O and CH₃CH₂OH as organic solvents.The effects of reaction time,temperature and pH of the solution on the morphology and dispersion of MSNs were investigated by FE-SEM.The results showed that reaction time,reaction temperature and pH of solution had great influence on the morphology and dispersion of MSNs,and MSNs with better monodispersity of about 50 nm were successfully prepared when the reaction time was 2 h,the temperature and pH of the solution were 50?and 11.5,respectively.?3?MSNs/CS was synthesized by a series of chemical reactions with GPTMS as bridge agent and CS as raw material.The methods of FT-IR,TGA,XRD and N₂ adsorption-desorption were used to investigate the concentration of CS on the composition of composites.The results showed that with the increase of CS concentration,although the more CS is in MSNs/CS,but the viscosity of CS also increases,which affects the synthesis of MSNs/CS.When the concentration of CS was 4%w/v,the FT-IR spectra of MSNs/CS showed the epoxy absorption peaks(at 463 and 875 cm^-1)and the CH₃ tensile vibration absorption peaks(at 2950 and 2907 cm^-1);Analysis and comparison of FT-IR and TGA spectra of MSNs and MSNs/CS showed that MSNs/CS hybrids were successfully prepared using GPTMS as a bridging agent.The TGA spectrum of MSNs/CS showed that weight loss occurred at 300?due to the decomposition of the amino group of chitosan;The XRD pattern showed that the broad peak characteristics of the amorphous material are retained,and the peak position of the material was almost unchanged;The N₂ adsorption desorption isotherm curve was in accordance with the type?isotherm,and there is an obvious step between P/P₀ 0.1 and 0.3.It was shown that when the CS concentration was 4%w/v,MSNs/CS with a good mesoporous structure and a particle size of about 60nm were successfully synthesized.?4?The drug loading and release properties of MSNs and MSNs/CS materials were studied using DOX·HCl as a model drug.The results showed that the drug loading and encapsulation efficiency of MSNs/CS were 32.47±0.478%and 96.164±0.0643%,respectively,which were much higher than those of MSNs?15.34±0.54%and 36.25±0.126%,respectively?.The drug release amount of MSNs/CS-DOX·HCl in 24 hours?50%?is higher than that of MSNs-DOX·HCl?30%?when pH was 5,and the drug release time of the former is even extended to 144 h.Moreover,the in vitro drug release curve of MSNs/CS is highly fitted to the Higuchi equation,which indicates that the MSNs/CS-DOX·HCl system has pH response and sustained-release characteristics.?5?In this paper,HepG2 hepatoma cells and HL-7702 normal-hepatic cells were used as cell lines.The biocompatibility of the materials was studied by hemolysis test,MTT test and inverted fluorescence microscope.The results of hemolysis experiment showed that when the concentration of MSNs/CS was as high as 2 mg/mL,the hemolysis rate was still lower than 5%.MTT results showed that when the concentration of MSNs/CS reached 250?g/mL,the cell survival rate of the carrier material was still greater than 80%.The cell death rate of cells treated with MSNs/CS-DOX·HCl was lower than that of cells treated with free DOX·HCl at the same concentration after 48 h.The experimental results of cell uptake and intracellular drug release of MSNs/CS-DOX·HCl delivery system showed that MSNs/CS-DOX·HCl can release DOX·HCl in HepG2 hepatoma cells but not in HL-7702 normal hepatic cells.It was shown that MSNs/CS synthesized with GPTMS as a bridging agent can significantly improve the selective therapeutic effect of DOX·HCl on cancer cells,and the results of the study will provide new ideas for the development of targeted sustained-release preparations.