Studies On PH And Glucose Responsive Controlled Release System Based On Mesoporous Silica Nanoparticles

Drug controlled release system could reduce the leakage in the process of transport and the side effects of drugs, then released the drugs after arrive in focus location, which could improve efficacy of drugs, so it had wide application prospect in biomedical field. With the continuous development of nanotechnology, many nanomaterials were used to construct functional drug carriers for the treatment and researches of diseases. Mesoporous silica nanoparticle(MSN) is a kind of good drug carrier, because it has high specific surface area, adjustable size and aperture, easy synthesised and modified, biocompatibility and many other features. In recent years, in order to meet the development of the modern medical of controlled release drugs in lesions, a lot of controlled release drug systerms stimulated by pH, temperature, light, small molecules, magnetic field have been developed. The pH value of human’s different organizations is different. Such as the pH value of cancer cells and inflammatory tissues is lower than normal tissue and blood, and the pH of lysosome and the endosome are the lowest. In addition, diabetes, which continuously has higher concentration of blood glucose than normal and would lead to a variety of complications, has been a serious threat to people’s health. Tumor can cause abnormalities of blood glucose, and diabetic patients’ sustained high blood glucose can lead to increased risk of malignancy tumor. Therefore, the construction of pH and glucose double responsive controlled release system has an attractive potential applications in the treatment of disease and it has great significance. This paper aimed at construction of pH and glucose responsive controlled release system by using MCM-41-type MSN as carriers and polymer as blocking agent developed two types of pH and glucose responsive controlled release systems. The main content as follows:(1) Study on pH and glucose responsive controlled release system based on polyhydric polymer gated mesoporous silica nanoparticlesUsing dextran with cis-1,2-dihydroxy and polyvinyl alcohol with cis-1,3-dihydroxy as gated agent and benzene boric acid modified mesoporous silica nanoparticle as carrier designed two kinds of pH and glucose responsive controlled release systems. The results showed that the polyhydric polymer could gate the pore of mesoporous silica nanoparticles. The release rate and quantity of the object molecules could be influenced by pH and glucose concentration. When the pH of the solution was lower or the concentration of glucose was higher, the release rate and quantity of the object molecules was bigger. It was a good dual-responsive system, and the system had a good biological compatibility. It could provide a new opportunity for the treatment of cancer and diabetes research.(2) Study on pH responsive controlled release system based on p(DMAEA-VPBA) blocked mesoporous silica nanoparticlesUsing the method of situ polymerization of two sensing elements, acrylic acid 2-(dimethylamine)ethyl ester(DMAEA) and p-vinyl benzene boric acid(VPBA), modificate to the surface of mesoporous silica nanoparticles by covalent to build a series of pH and glucose responsive controlled release systems. Due to DMAEA contains tertiary amine groups and under acid condition it can be combined with protons. Thus under acid condition, polymer chain would be positively charged which could make the polymer repelling each other and increase the hydrophilic of polymer, then it would lead to the open of the pore of MSN and the release of dye moleculers. Because the proton of the tertiary amine group is reversible, it could switch on and off the pore by reversibly changing the pH valus, then regulate the state of the “gate”. The formation of B???N bond between boron atom of VPBA and nitrogen atom of DMAEA could enhance the interaction between polymer chains of particle surface, and reduce the leakage of object model molecules. In addition, using the reaction between benzene boric acid and small molecular polyol could further increase the surface density of polymer of the particles and reduce the gaps between the polymer chains. Then it reduced the leakage of dye molecules in the alkaline conditions, and improved the performance of the release of the carrier. Cell toxicity test showed that this system had good biocompatibility. It would provide a new way of reducing drug leakage when design pH responsive controlled release system, which based on polymer gated mesoporous silica nanoparticles.