Preparation And Evaluation Of Resveratrol-loaded Mesoporous Silica Nanoparticles Modified By Amino&cell-penetrating Peptide

Objective In order to improve the bioavailability of resveratrol(RES),resveratrol-loaded mesoporous silica nanoparticles modified by amino&cell-penetrating peptide(CPPs&NH2-MSN-RES)were prepared and evaluated,for providing the rationale of RES oral nanoparticles.Methods Selecting HPLC to establish the content analysis of RES.Mesoporous silica nanoparticles modified by amino(NH2-MSN)were synthesized by the modified Stober method.The formation was optimized in terms of orthogonal design based on single factor analysis including reaction temperature,reaction pH,rotate speed,CTAB concentration,volume of TEOS,volume ration of TEOS and APTES.Subsequently,CPPs was covalently conjugated onto NH2-MSN.Morphology was observed by transmission electron microscope(TEM),and laser particle size analyzer were used to determine the size and Zeta potential.Fourier transform infrared(FT-IR)spectra was to determine function of the amino;Small angle X-ray diffraction(XRD)was used to determine the mesoporous structure;nitrogen adsorption was used to calculate the surface area,pore diameter and pore volume;thermogravimetric analysis(TGA)was used for obtaining the grafting ratio and DL.By introducing the innovative preparation process of repeatedly saturated solution adsorbing method,RES was highly encapsulated into CPPs&NH2-MSN.By using dialysis bag method to investigate the in vitro drug release characteristics and MTT method to investigate the cytotoxicity on Caco-2 cells.The transport ability of the carrier was investigated by the Caco-2 cells monolayer model.Finally,pharmacokinetics behavior of CPPs&NH2-MSN-RES after oral administration in rats was studied.Femoral artery and jugular vein catheterization technology were used to collect blood samples;plasma concentration was determined by HPLC.Results Selecting HPLC to establish the content analysis of RES and the calibration curve showed a good linear relationship in the concentration range of 0.25～10μg·mL-1.MSN were prepared by the optimum formulation:reaction temperature was 80℃,reaction pH was 12.5,rotate speed was 1300 rpm,CTAB concentration was 0.2%,3 mL TEOS,volume ration of TEOS and APTES was 1.5:1.The distribution of CPPs&NH2-MSN was uniform,the average particle size was101.6±2.3 nm and the Zeta potential was 21.9±1.5 mv.CPPs&NH2-MSN had no obvious toxicity on Caco-2 cells.After 8 times adsorption repeatedly,the drug loading of CPPs&NH2-MSN-RES reached up to 19.15%.In drug release experiment,the cumulative release quantity of CPPs&NH2-MSN-RES was 70.8%within 48h,indicating sustained-release characteristics.CPPs&NH2-MSN-RES had a good ability of transmembrane transport on Caco-2 cell monolayer model,and the two-way apparent permeability coefficient(Papp)was much larger than the RES solution.In pharmacokinetic studies,the carrier had changed the pharmacokinetic characteristics of RES,RES was single chamber model in RES solution,whereas,RES was second chamber model in carriers.The AUC0-t of CPPs&NH2-MSN-RES was approximate 2.87-fold compared to that of RES solution,what’s more,T1/2,Tmax and Cmax of CPPs&NH2-MSN-RES was significantly greater than that of RES solution.Conclusion NH2-MSN were synthesized by modified Stober method successfully.Repeatedly saturated solution adsorbing method could effectively improve the drug loading.CPPs&NH2-MSN-RES improves the bioavailability of RES prominently.CPPs&NH2-MSN will be a promising nano material for oral drug delivery carrier.