| Diabetes is a global health problem.In clinical practice,type Ⅰ diabetes is mostly treated by injecting insulin to stabilize blood glucose level,which may bring about a series of health issues such as hypoglycemia and tissue damage.Stimuli-responsive materials are widely used in drug controlled release systems due to their variable behaviors under different circumstances.Glucose-responsive systems play a vital role in the controlled release of insulin because they can smartly adjust the amount of released insulin in response to the fluctuational blood glucose concentration.Among various systems,the phenylboronic acid-based systems draw much attention in virtue of their good controlled insulin release performance.Among various carriers,mesoporous silica is one of the most competitive materials used in stimuli-responsive drug release systems because of its ease of modification,large specific surface area and large pore volume.In mesoporous silica-based systems,insulin are often loaded in the pores of mesoporous silica.The controlled release of insulin is mainly achieved by imposing resistance to the spontaneous process of insulin diffusion.And the resistance often changes with the alteration of the surrounding glucose concentration.In this paper,three insulin release systems consisting of phenylboronic acid and mesoporous silica were prepared in which phenylboronic acid was used as the glucose-responsive unit and mesoporous silica was used as the drug carrier.And their glucose-responsive performance was studied.1)The mesoporous silica(MS)was prepared by the templating method.Then the MS was modified with amino groups to prepare aminated mesoporous silica(MS-NH2).After that,MS-NH2 was modified with 3-fluoro-4-carboxyphenylboronic acid(FCPBA)to prepare phenylboronic acid-modified mesoporous silica(MS-FCPBA).Acryl chloride and glucosamine were used to synthesize N-acryloyl glucosamine(AGA).AGA was copolymerized with N-isopropyl acrylamide(NIPAM)and acrylic acid(AAc)to synthesize two polymers with diol groups,noted as P(NIPAM-co-AGA)and P(AAc-co-AGA)respectively.Since the phenylboronic acid group can form a borate ester bond with the diol group,the polymers were coated on the surface of insulin-loaded MS-FCPBA to obtain the insulin release systems,noted as MS-FCPBA/Ins/P(NIPAM-co-AGA)and MS-FCPBA/Ins/P(AAc-co-AGA)respectively.The results showed that the loading capacity and encapsulation efficiency of insulin could reach 14.7%and 85.9%,respectively.And the MS-FCPBA/Ins/P(NIPAM-co-AGA)exhibited a sensitive glucose-responsive insulin release behavior.Due to the reversibility of borate ester bond,the diol structures of glucose are capable of breaking the original borate ester bond,resulting in the desorption of P(NIPAM-co-AGA)and the acceleration of insulin release.In contrast,MS-FCPBA/Ins/P(AAc-co-AGA)had almost no glucose-responsive behavior.It is believed that this difference was ascribed to the hydrophilicity-hydrophobicity of the polymers.The hydrophilicity makes P(AAc-co-AGA)unable to restrict the diffusion of insulin,and easier to desorb.2)Dendritic mesoporous silica(DMSN)was prepared by the biphase stratification approach.FCPBA was modified on the hydroxypropyl chitosan(HPCS)to obtain phenylboronic acid-modified hydroxypropyl chitosan(HPCS-FCPBA).In a weakly acidic environment,insulin was loaded on the DMSN,and the loading capacity and encapsulation efficiency could reach 32.1%and 94.6%,respectively.After that,HPCS-FCPBA was coated on the insulin-loaded DMSN to obtain an insulin release system DMSN/Ins/HPCS-FCPBA.Then sodium alginate was coated on DMSN/Ins/HPCS-FCPBA,followed by calcium ion crosslinking to obtain another insulin release system DMSN/Ins/HPCS-FCPBA/SA/Ca.The results demonstrated that both systems had excellent performance in sustained insulin release.For DMSN/Ins/HPCS-FCPBA,The desorption of HPCS-FCPBA showed obvious glucose-responsive behavior.For DMSN/Ins/HPCS-FCPBA/SA/Ca,the cumulative release of insulin did not exhibit any glucose-responsive behavior.According to the desorption of HPCS-FCPBA and the release behavior of insulin in these two systems,we believe that the polymer layer causes a certain resistance to the insulin release process.And the desorption of HPCS-FCPBA can reduce the resistance,leading to the acceleration of the insulin release.3)Dendritic mesoporous silica(DMSN-T)was prepared by the biphase stratification approach,and the surface of DMSN-T was modified with amino groups to obtain aminated mesoporous silica(DMSN-NH2).The sodium alginate was modified with 2-aminophenylboronic acid to attain phenylboronic acid-modified sodium alginate(SA-APBA).Insulin was loaded on DMSN-NH2 to obtain insulin-loaded DMSN-NH2(DMSN-NH2/Ins),and the loading capacity and encapsulation efficiency of insulin could reach 32.9%and 98.1%,respectively.SA-APBA was mixed with a guar gum(GG)suspension of DMSN-NH2 and DMSN-NH2/Ins to prepare DMSN-NH2/SA-APBA/GG gel and DMSN-NH2/Ins/SA-APBA/GG gel respectively.The raw material ratio of the gel was adjusted by rheological test.The cumulative insulin release experiments were performed to study the glucose-responsive insulin release performance of DMSN-NH2/Ins/SA-APBA/GG gel.The results showed that the content of DMSN-NH2 affected the modulus of the DMSN-NH2/SA-APBA/GG gel,and the gel with the content of DMSN-NH2 less than 16 mg/cm3 owned good self-healing properties.In addition,the DMSN-NH2/Ins/SA-APBA/GG gel had a good sustained insulin release performance and exhibited evident glucose-responsive insulin release behavior. |
