Preparation And Application Of Mesoporous Silica/Chitosan Composite Nanoparticles

At present, the pharmaceutical industry faces enormous challenges: the discoveryof innovative drugs is increasingly difficult, and the success rate of new drugdevelopment is low in various aspects. Therefore, the cost for research anddevelopment of innovative drugs is becoming higher and higher. But to some extent,this situation provides more opportunity for development of pharmaceuticalpreparations. The development of novel drug delivery system has attracted increasingattention for unique properties, in which nanoparticles based on nanotechnology havebecome a hot topic of research. This dissertation includes three main parts: In the firstpart, based on the P123as a template agent the mesoporous SiO2nanoparticles havebeen synthesized quickly with uniform particle size and good morphology in whichprecipitation was induced by phosphate buffer. The second part provides a fast andefficient method of activating mPEG through on-line FTIR process analyticaltechnology and grafting activated mPEG onto the chitosan6-OH by chemicalmodification in order to form the soluble copolymer. Furthermore, the copolymer isused to prepare nanoparticles by emulsification and self-assembly technology.Thethird part is mainly the synthesis of silica/chitosan composite nanoparticles. We givethe prepared materials characterization and analysis in each part, and hope tosynthesize nanomaterial that has potential applications in enzyme immobilization andcontrollable release of drugs.Polyamines, surfactants and copolymers can be used as the template to synthesizemesoporous materials. We use P123as a template to develop a method that phosphatebuffer solution induce the synthesis of the ordered structure （p6mm） and "onion"-likemesoporous SiO₂（TJU-X） to overcome the traditional method of time-consumingconsumption the determination of their pore size of4.2-8.0nm, a pore volume of0.72-0.96cm^-3/g, specific surface area of410-740m^-2/g. The reaction takes place andcomplete at25℃within10min. The activity of immobilized pepsin is680.2U/gand enzyme immobilization rate62.76%. In situ embedded pepsin, The activity ofimmobilized pepsin is425.4U/g and enzyme immobilization rate is90%.We develop the method to activate mPEG through the online infrared FTIR. Andthen make the activated of mPEG graft onto chitosan6–OH for synthesis of PEG-CS. The application of online FTIR process analysis tools short the cycle time of reactionand improve the yield. The copolymer of PEG-CS/TPP can get to the formation ofnanocarriers by polyion role in the microemulsion environment. The nanocarrers havea good load performance to Ibuprofen.On the basis of the synthesis of PEG-CS aforementioned, glutaraldehyde is usedas the crosslinking agent to prepare chitosan-coated silica composite nanoparticles.And by adding silica nuclear composite nanoparticles SiO2@PCS with pH sensitivityhave been completed. What’s more, nature of the materials is tested by means of SEM,TEM and IR. The composite nanoparticles show good adsorption andcontrolled-release function to BSA（bovine serum albumin）.