| Oral administration is an ideal way of administration with convenience and good patient compliance.However,oral administration must expose to experience harsh gastrointestinal tract,which leads to poor drug efficacy.Because of its hydrophobicity,biocompatibility,resistant to acid and digestive enzymes,Zein is considered to be excellent carrier for oral administration.But poor stability under physiological environment limits the application of Zein in biomedical.In this work,indomethacin(Indo)was selected as the model drug,and the succinic anhydride(Suc)and zeolitic imidazolate framework-8(ZIF-8)were used to modify Zein particles to overcome these shortages.The main contents are as follows.First,succinylated-Zein(Suc-Zein)was synthesized by nucleophilic substitution reaction and characterized by FTIR,~1H NMR,etc.Suc-Zein nanoparticles(SZs)and Indo-SZs were prepared under the conditions optimized by orthogonal experiment using the Built-in Ultrasonic Dialysis Process(BUDP).The results showed that the particle size,size distribution,pH stability,ion stability,storage stability and resuspension of SZs particles were better than Zein particles.More importantly,Indo-SZs had sustained drug release in simulated physiological and gastrointestinal environment.Cytotoxicity test showed that SZs was non-cytotoxic,while Indo-SZs had obvious cytotoxicity for A549 cells.Second,Indo-ZIF-8 was synthesized by aqueous phase method.Then the core-shell compact spherical particles(Indo-SZZs)were prepared by mixing Indo-ZIF-8 and Suc-Zein in BUDP.The results indicated that Indo-SZZs had pH-response characteristics and sustained drug release in simulated physiological and gastrointestinal environment.Cell experiments showed that Suc-Zein-ZIF-8 was non-cytotoxic and could be well uptaken by cells with good biocompatibility,while Indo-SZZs had obvious cytotoxicity for A549 cells.The results would provide new insight for construction of Zein-based oral drug delivery system. |
