| Mesoporous silica have the advantages of easy regulation,high biocompatibility,good degradability,and low cost.They can be used as drug delivery carriers to improve pharmacokinetics and pharmacodynamics.By adjusting the structural parameters such as particle size,pore size,morphology and internal structure,the sustained release performance of drugs can be changed to meet the sustained release needs of different drug.The innovation of this paper is the preparation of mesoporous silica with different pore sizes using methylene blue as a structural modifier,and the successful preparation of core-shell mesoporous silica of different core sizes by adjusting the number of silicon source additions,using propranolol hydrochloride(PNH)as a model drug,loaded in mesoporous silica,to explore the structure-activity relationship between mesoporous silica structure and PNH sustained release performance.Mesoporous silica nanomaterials(MSN)with a particle size of about 180 nm and pore size distribution range of 2.6-3.2 nm were prepared by the sol-gel method.Yolk-shell mesoporous silica nanomaterials(YSMSN)with a diameter of about 180 nm,shell thickness of 20 nm,core size of 110 nm,and aperture distribution of 3.7 nm were prepared by sodium carbonate selective etching method.Hollow mesoporous silica nanomaterials(HMSN)with a diameter of about 180 nm,shell thickness of 30 nm and aperture distribution of 3.2 nm were prepared by sodium carbonate selective etching method.YSMSN with different particle sizes and core sizes were prepared by adding silicon source again.PNH-loaded mesoporous silica composite particles(MSN@PNH,YSMSN@PNH,HMSN@PNH)were prepared by dry dipping.The effect of methylene blue(MB)on the structure of MSN and the effect of1,3,5-triisopropylbenzene(TIB)on the pore size of HMSN were investigated.The results show that,with the increase of MB addition,the proportion of characteristic holes of MSN at 2.6 nm gradually decreases,the proportion of characteristic holes at 3.2 nm gradually increases,and the specific surface area increases from 1 055 m2/g to 1 229 m2/g,which proves that MB can increase the pore size and specific surface area of MSN.With the increase of TIB addition,the pore size of HMSN gradually increased from 3.2 nm to about4.8 nm,and the pore size distribution range gradually increased,when the TIB addition exceeded 0.05 g,the pore size distribution of HMSN no longer changed,but its specific surface area gradually decreased.The drug loading of mesoporous silica of different structures prepared by dry dipping,and the effect of different drying methods on drug load was investigated.The results showed that vacuum drying had a larger drug load than atmospheric pressure drying,and the drug load of HMSN increased from 187 mg/g to 234 mg/g with the larger the internal cavity of mesoporous silica.It can be seen from the change of drug load of mesoporous silica with different structures that when the pore size increases from 2.9 nm to 3.2 nm,the drug load increases by 71%,and when the pore size is further increased,the increase of drug load gradually slows down.Moreover,with the gradual increase of the internal cavity of mesoporous silica,its drug load gradually increased,and HMSN had the largest drug load of 234 mg/g.The drug release performance study showed that by adjusting the structure of mesoporous silica,a series of drug-loaded particles with different sustained release properties were prepared,and the drug sustained release time was 6-14 h.The larger the pore size,the faster the drug release,the shorter the time to reach the release equilibrium,the best sustained release performance of the prepared YSMSN@PNH-loaded drug particles,and the larger the core,the longer the drug release time.The sustained release process of mesoporous silica of the three structures conforms to the first-order kinetic model,indicating that PNH and mesoporous silica have no chemical force,and drug release is a simple diffusion process. |
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