Preparation And Drug Release Of PH-responsive Mesoporous Silica Nanotubes By Electrospun Silk Fibroin Nanofibers As Templates

In recent years,the nano-drug delivery system as a new drug delivery technology has made great progress in biomedical field.It mainly means that the drug is loaded into the nanocarrier and controlled release of the drug can be achieved through stimulation of the external environment or self-degradation.The biggest advantage of this method is that it can target diseased tissue and release the drug continuously.This targeted treatment can not only improve the concentration of local drugs,but also control the concentration of drugs in other parts of the body and reduce the toxic and side effects on normal tissues.Hollow mesoporous silica materials,because of the cavity and mesoporous structure,large specific surface area,good stability and biocompatibility,easy modify surface etc,shows the great application prospect in nano-drug delivery system.Among these materials,Mesoporous Silica Nanotubes,MSNTs,are of particular interest to researchers,because it has the characteristics of anisotropy and large aspect ratio in addition to the above characteristics.Generally,the template used to prepare MSNTs includes block polymer assembly and columnar polymer brush,etc.However,the above template preparation process is complex and expensive,which makes it impossible to realize mass production of MSNTs.Therefore,in this paper,silkworm silk fibers with abundant resources and low cost was used as raw material to prepare silk fibroin(SF)fiber templates by utilizing the advanced technology of electrospinning,which is an efficient method for preparation of micro-nano fibers.Silica were coated on the surface of SF fibers by sol-gel process,and MSNTs were obtained after the templates were removed by calcining.On the other hand,on account of stimulus-responsive mesoporous silica nano-targeted drug delivery system is a hot topic in recent years.In this study,aldehyde groups were grafted on the surface of MSNTs,the pH sensitive dynamic covalent bond was formed between the aldehyde group and the amino group in DOX,the pH responsive of the system of MSNTs-CHO-DOX were investigated.The main results of this paper are as follows:(1)Regenerated silk fibroin solution containing fibroin microfibers was obtained by dissolving degummed silk fibers in calcium chloride/formic acid system through destroying the multistage structure of the original silk fibers.One-dimensional silk fibroin nanofibers were prepared by electrospinning.The SEM results showed that when the concentration of regenerated silk fibroin/formic acid solution was between 21~25%,silk fibroin nanofibers with diameters of 113±27~134±32 nm could be prepared.(2)Electrospun silica/SF composite fibers were prepared by sol-gel process with electrospun SF fibers as hard templates.MSNTs were obtained after the hard template was removed by calcining.After characterized by FTIR,SEM and EDS,the SF templates in MSNTs was basically removed.Changing the amount of CTAB in the coating solution,the wall thickness of the prepared MSNTs were characterized by SEM and TEM.It was found that when the addition amount of CTAB in the solution increased from 1.25 to 3.75 mg/mL,the wall thickness of the corresponding MSNTs increased from 30~39 nm to 63~65 nm,indicating that the wall thickness of MSNTs could be adjusted by adjusting the amount of CTAB in the solution.BET analysis showed that the specific surface area of the corresponding MSNTs decreased from 154 m~2/g to 98 m~2/g,pore volume decreased from 0.49 cm~3/g to 0.23 cm~3/g,and the average mesoporous diameter decreased from 12.5 nm to 9.9 nm.(3)The amino and aldehyde groups were grafted in turn on the surface of MSNTs,and MSNTs be functional aldehyde groups(MSNTs-CHO)were confirmed by FTIR.The pH-sensitive mesoporous silica nano-drug delivery systems(MSNTs-CHO-DOX)were obtained by Schiff base reaction between the aldehyde groups on the silicon nanotubes and the amino groups in DOX.By testing the drug release behavior of MSNTs-CHO-DOX systems under different pH conditions,it was found that the release rate of DOX was the slowest,23%at100 h,in PB buffer solution at pH 7.4.In the PB buffer solution at pH 6.5 and 5.4,the carbon-nitrogen double bond was hydrolyzed,and the release of DOX can reached 35%and 75%at 100 h respectively,and achieving the pH responsive release of the MSNT-CHO-DOX drug delivery systems.In summary,this study provides a simple,efficient,and low-cost new method for the preparation of mesoporous silica nanotubes by improving preparation techniques and raw materials.At the same time,by skillfully utilizing the characteristics of the amino group in the drug and aldehyde groups on the surface of MSNTs to form a pH-sensitive dynamic covalent bond,realizing the pH-responsive release of the drug itself as a "gated switch".