Mesoporous Silica Nanoparticles: Preparation And Application In Drug Delivery System

Due to the unique properties of nanomaterials,Mesoporous silica nanoparticles(MSN)play an important role in the field of medicine,especially in the treatment of cancer.Compared with organic polymer nano materials,it has a large specific surface area and the entrance,adjustable pore size and shape,easy to modify the internal and external surface and good biocompatibility.At the same time,the unique optical,electric,magnetic properties given its potential imaging enhancement,targeted delivery and collaborative drug therapy,which makes it becomes one of the most promising drug carrier.There are many types of mesoporous silica nanoparticles can be prepared by controlling the conditions of different models,such as MCM-41,MCM-48,SBA-15 etc.In this paper,two different kinds of mesoporous silica(SBA-15 and MCM–41)were loadedwiththree kinds of different properties of drugs,to investigate their potential applications in drug delivery.All the relative studies are outline as follows.(1)To establish an analytical method of EXT in vitro,SBA-15 mesoporous silica nanoparticles as a carrier material.EXT-SBA-15 was prepared by dipping adsorption method,and its in vitro drug release characteristic was investigated.EXT-Sol as the control group,in vivo pharmacokinetic was investigated after subcutaneous injection of EXT-SBA-15.Exendin-4 ELISA kit was used to determine the content of EXT at different time points in mice,PK Solver 2.0 pharmacokinetic software wasused to calculate pharmacokinetic parameters,to investigate the drug release of EXT-SBA-15.We used diabetic mice as model animals,set up blank control group,model control group,EXT-Sol group,EXT-SBA-15 group and blank SBA-15 group,a preliminary hypoglycemic effect investigation of diabetes mice after subcutaneous injection of EXT-SBA-15 was to carry out.This study succeeded in preparation of EXT-SBA-15,the preparation process was simple,with a higher drug-loading rate.Studies in vivo and in vitro had shown that EXT-SBA-15 can extend drug residence time in the body,had obvious sustained release characteristics and hypoglycemic effect,which was expected to become a promising and ideal carrier of exentide.This research provided the experimental basis and theoretical reference for the application of the mesoporous silica materials such as SBA-15 and the peptide drugs research and development of controlled-release formulation.(2)PAA was covalently attached to the exterior surface of amino group functionalized MSNs prepared by co-condensation method and ATO was loaded into them by electrostatic adsorption.The formation was optimized in terms of orthogonal design based on single factor analysis including reaction temperature,reaction pH,CTAB concentration,volume of TEOS,volume ration of TEOS and APTES.Morphology was observed by transmission electron microscope(TEM)andscanning electron microscope(SEM).Small angle X-ray diffraction(SAXRD)was used to determine the mesoporousstru cture;nitrogen adsorptionwas used to calculate the surface area,pore diameterand pore volume;Fourier transform infrared(FT-IR)spectrawas to determine function of the amino and PAA;thermogravimetric analysis(TGA)was to calculate the grating ratio and laser particle size analyzer were used todetermine the size and Zetapotential.The Entrapment efficiency and drug loadingof PAA-ATO-MSNs were investigated with the method of high speed centrifugation combined with inductively coupled plasma emissionspectrum(ICP).The drug release behavior of PAA-ATO-MSNs was studied using dynamic dialysis method,PBS(pH 5.0,6.0 and 7.4)chosen as release medium.SMMC-7721 cells in vitro model was constructed to evaluate inhibition rate of tumor cells and cycle arrest.And H22 in vivo modelwas constructed to evaluate inhibition rate of tumor cells.Pharmacokinetics behavior of PAA-ATO-MSNs after intravenous injection in rats was studied.Femoral arteryand jugular vein catheterization technology were used to collect blood samples;plasma concentrationwas determined by inductively coupled plasma mass spectrometry(ICP-MS).PAA-ATO-MSNswere successfullyprepared with small size,higher EE and DL.Release of ATO from PAA-ATO-MSNs showed the obvious p H-responsive characteristic and sustained-release in vitro and PAA-ATO-MSNs had improved the pharmacokinetics behavior in rats.PAA-MSNs might be promising carrier to load ATO for cancer therapy.The antitumor efficacy in vitro andin vivo was remarkably enhanced indicated that PAA-ATO-MSN improved the antitumor effect of thedrug.(3)In order to improve the drug loading coefficient and realize the targeting delivery of paclitaxel(PTX)to brain and glioma,a novel core-shell structural phospholipid-functionalized mesoporous silica nanoparticles(MSN-LP)modified with Angiopep-2(ANG-MSN-LP)were successfully developed using selfassembly and film hydration method,and mesoporous silica nanoparticles(MSN)synthesized by modified-Stober method as control.By introducing the innovative preparation process of saturated solution adsorption method,PTX was highly encapsulated(drug loading efficiency up to 11.17%)into MSN(MSN-PTX)by forming crystal analogue complex inside the mesoporous pore channels.The results of in vitro release showed that about 75.5% of PTX released from ANG-MSN-LP-PTX(PTX loaded into ANG-MSN-LP)after 50 h and burst release was effectively reduced comparedwith MSN-PTX or PTX solution,indicating pronounced sustained-release characteristics.The biological safety of ANG-MSN-LP was evaluated by HBMEC and C6 cells,which proved ANG-MSN-LP had good biocompatibility and low toxicity.Compared to the control PTX formulations of MSN-PTX,MSN-LP-PTX(PTX loaded into MSN-LP)and PTX solution,ANG-MSN-LP-PTX was proved to increase the transport ratio of the PTX across the BBB and afterwards target the brain glioma and displayed higher cell uptake,stronger growth inhibition and apoptosis of glioma cells,better curing effect on glioma,and improved MST of C6 cells-implanted rats.Additionally,in pharmacokinetics by using blood and intracerebral microdialysis simultaneously,the AUC intracerebral of ANG-MSN-LP-PTX was increased to approximate 5.29-fold compared to that of PTX solution,but the AUCblood 2.85-fold.However,the most surprising discovery is that the concentration-time curve of injected ANG-MSN-LP-PTX and MSN-LP-PTX tended to be similar to oral administration,which indicating that the nanoparticles as drug reservoirs can be detained in blood.In conclusion,ANG-MSN-LP is a prospective targeting drug delivery system for therapy of brain glioma.Meanwhile,saturated solution adsorption method can increase the drug loading efficiency highly,blood and intracerebral microdialysis simultaneously can demonstrate the genuine capacity of brain targeting drug delivery system and precise pharmacokinetics of drug loaded in nanoparticles.