Preparation And Properties Of Metformin Hydrochloride-loading Hollow Mesoporous Silica Nanoparticles

In recent years,nano-drug delivery systems have been widely used in the field of biomedicine,to achieve targeted delivery of drugs at site of action,improve the bioavailability of drugs and reduce the drug toxicity.Hollow mesoporous silica nanoparticles(HMSN)have received extensive attention in the biomedical field owing to their high Specific surface area and large pore volume,as well as ease of modification and good biocompatibility.On this basis,the main purpose of this study was to prepare a metformin hydrochloride(Met)-loaded hollow mesopore silica targeted drug delivery system,which could be used to load metformin hydrochloride in the hollow cavity,and could target tumor cells and improve the killing effect on tumor cells due to the functionalized modification of folate(FA)on the surface of HMSN.This thesis mainly includes the following three aspects:1.HMSN nanoparticles were prepared by hard template method and selective etching method,and the prepared HMSN was characterized by SEM,TEM,laser particle size analyzer,etc.The results showed that the average hydrated particle size is131nm,PDI is 0.113,and Zeta potential is-10.3mv,The morphology is regular and spherical,the particle size is uniform,and the dispersion is good.The particle size is approximately 120nm,and the hollow cavity diameter is approximately 100nm;infrared spectroscopy results showed that HMSN has a typical silicon-based skeleton characteristic absorption peak;the mesoporous structure is arranged in an orderly manner.The specific surface area is 1080.576m~2/g,the mesopore pore size distribution curve is narrow,the average pore size is 3.047nm,and the pore volume is 0.902cm~3/g.2.Modification of HMSN to generate HMSN-FA,and introduction of FITC to the surface of HMSN and HMSN-FA to generate HMSN-FITC and FA-HMSN-FITC.The functionally modified HMSN nanoparticles were characterized by TEM,dynamic laser scattering,infrared spectroscopy,and fluorescence spectroscopy.The nanoparticles are spherical,with a particle size of approximately 120nm,an internal hollow structure is obvious,and the external mesoporous shell is complete.According to the Met standard curve,the drug loading of Met@HMSN nanoparticles is 245.2μg/mg,and the encapsulation rate is 16.25%.The drug loading of Met@HMSN-FA nanoparticles is233.7μg/mg,and the encapsulation rate is 15.25%.The drug-loaded nanoparticles have a relatively fast release rate during the initial release period(0-24 h),while within 24-36h,the release rate of the drug is relatively slow.Nanoparticles exhibited a sustained release.After 12h,the drug release rate reaches 34-44%,and the drug release rate can reach 55-71%,after 36h.3.In vitro safety evaluation of the prepared HMSN and HMSN-FA nanoparticles and in vitro anti-tumor effect of the drug-loaded nanoparticles were performed.The results show that the concentration of nanoparticles is directly proportional to the hemolysis rate.At 400μg/m L,the hemolysis rates of HMSN and HMSN-FA are 54.14%and 12.42%respectively.According to the BSA standard curve equation,the protein adsorption rates of HMSN and HMSN-FA nanoparticles are 9.3%and 4.5%,respectively.Cytotoxicity results showed that the safe concentration range of HMSN and HMSN-FA nanoparticles is 0-200μg/m L,and the safty margin of HMSN-FITC and FA-HMSN-FITC nanoparticles is 0-100μg/m L.The anti-tumor effect of drug-loaded nanoparticles showed that,Met@HMSN,Met@HMSN-FA nanoparticles and free Met had little difference at 12h in killing tumor cells.At 24h,compared with free Met,the cell killing rate of Met@HMSN nanoparticles increased by 5%-7.5%,while the cell killing rate of Met@HMSN-FA nanoparticles increased by 12.9%-19.1%.FA-modified FITC-HMSN-FA nanoparticles can target Hela cells,and the uptake of nanoparticles by Hela cells is time-and dose-dependent.The uptake of nanoparticles increased with increase in dose and exposure time,The endocytic process might clathrin-mediated and energy depedent.