Preparation Of Functionalized Mesoporous Silica Composite Microspheres And Its Application In Drug Delivery

In recent years, mesoporous silica nanoparticles(MSNs) are concerned with the advantages of large specific surface area、tunable particle size、thermal stability and so on. It has broad application prospects in catalysis、adsorption and separation、sensors, especially in the biomedical field. MSNs have many advantages as drug carrier, for example, it has high drug loading, the surface of MSNs has a large number of silicon hydroxyl, it also has targeting effect, which is of great significance to improve the therapeutic effect and reduce the side effects. The environmental responsive drug delivery system will change with the change of environmental factors because of some physical or chemical properties, which will have a good application value in drug delivery system. In the past, Most work focusde on traditional vector system, and there was less research on the controlled drug release system. In this study, the environmental responsive mesoporous silica composite microspheres were prepared, and the controlled release of the drug was realized. It includes the following aspects:1. MSNs were successfully synthesized by sol-gel method with triethanolamine(TEA) as a alkaline catalyst. Subsequently, the mesoporous silica surface was modificed with a silane coupling agent 3-(methacryloxy) propyl trimethoxysilane(MPS), then MSNs@PMAA composite microspheres were synthesized by precipitation polymerization method with methacrylic acid(MAA) as raw material. Their structure and morphology were characterized by X-ray powder diffraction, fourier-transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analyzer and other characterization methods. The in vitro release test of MSNs@PMAA microspheres was studied using doxorubicin(DOX) as a model drug. Results showed that MSNs were spherical, and average diameter was 137 nm. After the polymer coating, the surface area, pore volume and pore size of MSNs were from 1081 m2/g、1.756 cm3/g、3.2 nm reduced to 506 m2/g、1.34 cm3/g、1.7 nm, respectively, thermal gravimetric analysis showed that the amount of polymer coating was 12.1%. In vitro release test showed that the cumulative release rate of DOX in 12 h was relatively fast, and then became slow, and showed a tendency to increase with the decreased of pH value. The maximum cumulative release rate of DOX was 35.1%、54.6%、66.4% with pH value at 7.4、6.8、5.5. The results showed that the MSNs@PMAA composite microspheres had obvious p H responsiveness in vitro.2. MSNs were successfully synthesized by sol-gel method. Subsequently, the mesoporous silica was modificed with a silane coupling agent MPS. Then MSNs@P(NIPAM-co-NHMA) composite microspheres was prepared through the facile precipitation polymerization method. Their structure and morphology were characterized by X-ray diffraction, fourier-transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analyzer and other characterization methods. The in vitro release behavior of MSNs@P(NIPAM-co-NHMA) microspheres to doxorubicin was investigated using doxorubicin(DOX) as a model drug. Results showde that MSNs nanoparticles were spherical, the average diameter was 84 nm, Polymer coating, MSNs specific surface area, pore volume and pore size were from 919 m2/g、1.53 cm3/g、3.1 nm reduced to 623 m2/g、0.96 cm3/g、2.1 nm, thermal weight loss analysis showde that polymer coating amount for 18.3%. In vitro release studies showed that the maximum cumulative release rate of DOX was 23.1% 、 34.1% 、 52.6% at temperatures of 25 、 32 and 40 ℃. The results showed that the MSNs@P(NIPAM-co-NHMA) composite microspheres had obvious temperature responsiveness in vitro.