Research On Mesoporous Silica Nanoparticles Functionalized With PEG Via A Disulfide Bond As Drug Delivery System

An ideal drug delivery system could transfer drug molecules to targeted area in controlled way. Mesoporous silica nanoparticles(MSNs) possess many attractive properties, such as good biocompatibility, high surface area, large volume, adjustable diameter and morphology. Kind of drugs could be loaded in the mesoporous channels to realize controlled release by external factors. More and more attention was paid to the MSNs which were used as drug delivery material. Polyethylene glycol(PEG) is a kind of good water-soluble material, having many advantages, such as favorable biocompatibility and biodegradability.Mesoporous silica nanoparticles functionalized with PEG via a disulfide bond used as drug delivery system was designed in our work based on the good properties of MSNs and PEG. Drugs could be controlled to release through stimulative-responsibility of the disulfide bond, which could provide scientific basis for the MSNs drug controlled release system.Thiol-functionalized mesoporous silica nanoparticles(MSNs-SH) were synthesized by co-condensation method in our project. Thiol-functionalized Me OPEG(Me OPEG-SH) prepared by Michael addition reaction was grafted to the MSNs-SH via a disulfide bond linker(MSNs-SS-PEG) as drug delivery material. Finally, doxorubicin(DOX) was used as a model drug to investigate its in vitro loading and release behavior. The dynamic light scattering(DLS), Fourier transform infrared spectrometer(FT-IR), transmission electron microscopy(TEM), field emission scanning electron microscopy(FE-SEM), nitrogen sorption analyzer, X-ray diffractometer(XRD) and ultraviolet spectrophotometer(UV) were used to characterize the experimental samples, the experimental results are as follows:(1) The MSNs-SH exhibited a relatively uniform spherical shape with an average diameter of about 140~160 nm. The typical â…£mesoporous structure could be observed, its specific surface area and pore volume were large.(2) Thiol-functionalized Me OPEG(Me OPEG-SH) was prepared by esterification reaction and Michael addition reaction. The FT-IR result confirmed that the thiol group was modified to the Me OPEG successfully.(3) After the Me OPEG-SH functionalization, the PEG-functionalized nanoparticles emerged better water solubility and dispersibility. Besides, the mesoporous structure remained stable and intact before and after the Me OPEG-SH modification. The MSNs-SS-PEG exhibited a relatively uniform spherical shape with large specific surface area as well as pore volume. DOX was effectively trapped in the mesoporous channels of the MSNs-SS-PEG without release after 24 hours. The drug loading efficiency and entrapment efficiency was 12.3% and 88.2%, respectively. However, when adding certain concentration of glutathione(GSH), the DOX was released from the mesoporous channels. The release profile of DOX from MSNs-SS-PEG exhibited a typical redox-responsive characteristic.In conclusion, the Me OPEG-SH was effectively functionalized onto the external surface of mesoporous silica, and the MSNs-SS-PEG could be used as a redox-responsive nano-drug delivery material.