Preparation And Application Of Surface Functionalized Hollow Silica Microspheres

Hollow silica microspheres(HMS)not only have a good biocompatibility,size adjustable,low toxicity,but also because of the large inner void,so that it has a greater specific surface area,put it can load more drug molecules.In addition,there are a large number of silyl groups on the surface of HMS,which are easy to be functionalized,and can obtain HMS composites with versatility.Therefore,HMS has broad application prospects in drug delivery system.In this paper,two kinds of hollow silica microspheres with stimulating response were designed and prepared to study the controlled release of drugs.Specific work is as follows:(1)Preparation of polyethylene glycol-polylactic acid modified magnetic hollow nanomaterials and its application.Firstly,polystyrene microspheres(PS)and Fe3O4/PS composite microspheres were synthesized,then,magnetic silica composite microspheres(SiO2/Fe3O4/PS)were prepared by using ethyl orthosilicate as the silicon source.After drying and calcination at high temperature,magnetic hollow silica composite microspheres(HMS)were obtained.Subsequently,the above-prepared magnetic composite microspheres were subjected to aminate and then polylactic acid(PLA)and polyethylene glycol(PEG)grafted magnetic hollow silica microspheres system HMS@PLA-PEG composite microspheres were fabricated.Transmission electron microscopy,infrared spectroscopy,ultraviolet-visible spectrophotometer,dynamic light scattering,thermogravimetric analysis and vibrating sample magnetometer were performed to measure the nanostructure and morphology of a series of different composite nanoparticles in the process of chemical reaction.The results show that we have prepared composite microspheres with uniform size,neat morphology and magnetic response.The contrast agent ioversol was successfully loaded by physical coating,drug release experiments was made at physiological pH.The results show that the drug loading rate was up to 39.4%and the cumulative release rate was 55.1%.Finally,the experiments of cytotoxicity exhibited that the carrier exhibited low toxicity when the concentration was as high as 400 ?g/mL,which can to ensure the safety of the carrier material.As a result,we can come to the conclusion that the cycle time was prolonged by slow release in the body and local concentration of ioversol was enhanced through the magnetic aggregation,which provided a good guarantee to improve the contrast effect in vivo.(2)Preparation of Mesoporous Silicon Nanoparticles with redox-response and its application in drug delivery system.First,hollow mesoporous silica microspheres(HMS)were prepared.by using homemade styrene microspheres(PS)and cetyltrimethylammonium bromide(CTAB)as co-templates.Then,it is alkynylated by a silane coupling agent and propiolate.At the same time,?-cyclodextrin was nitrided by two-step method.The ?-CD modified hollow mesoporous microspheres(HMS-CD)were prepared by "click reaction".Subsequently,the redox-responsive block polymer PEG-b-PPFc was prepared by atom transfer radical polymerization(ATRP)using polyethylene glycol as hydrophilic chain forging,hydroxyethyl methacrylate and ferrocene as hydrophobic chain.The structural characterization of different samples was carried out by infrared spectroscopy,nuclear magnetic resonance,transmission electron microscopy,dynamic light scattering,thermosgravimetric analysis and nitrogen adsorption-desorption isothermal test.The inclusion complexation and redox responsiveness of HMS-CD and amphiphilic block polymer PEG-b-PMAFc were analyzed by cyclic voltammetry,UV absorption spectroscopy and XRD.The results show that HMS-CD and PEG-b-PMAFc have been successfully assembled and have redox properties,which provide the possibility of real-time controlled release.To study the drug release behavior in the environment with different concentrations of oxidants(H2O2)with DOX as anti-tumor drug model.The experimental results show that DOX@HMS-CD@PPFc is very stable without adding H2O2,but adding 1 mL 30%H2O2,the cumulative release rate of drug is close to 52.1%within 12 h,indicating that in the oxidized environment drug delivery system,the drug release rate more quickly and with higher release rates.These results suggest that the self-assembly of cyclodextrin and ferrocene can effectively achieve the blocking of drugs and release the loaded drugs in the presence of H2O2.The release rate is positively correlated with the concentration of H2O2.Second,we used MTT to study the cytotoxicity of HMS-CD @PPFc and DOX @ HMS-CD @ PPFc.The results showed that the concentration of HMS-CD@PPFc increased from 25 ?g/mL to 100 ?g/mL,and the survival rate of HeLa cells remained at a high level,indicating that the blank carrier was not cytotoxic as a drug carrier.DOX@HMS-CD@PPFc has a high inhibitory rate for HeLa cells,as the concentration increasing,the inhibition rate also increased accordingly,indicating that it has good anti-cancer effect and has certain application prospect in biomedical field.In vitro study demonstrated that the HMS-CD@PPFc was highly biocompatible and suitable to use as drug carrier.Therefore,the redox-responsive HMS systems hold potential as a smart nanocarrier for anticancer drug delivery.