| Objective: Under the traditional administration mode,many drugs release rapidly,and the phenomenon of "peak and valley" is serious.Among the existing drug carriers,such as organic materials: liposomes and microspheres,inorganic materials: such as zeolite and ferric oxide,have not yet solved the above problems.Depending on the advantages of Metalorganic frameworks(MOFs),such as porosity,high drug loading and modifiability,in this paper,ZIF-8 and Zn-BTC were choosed as drug carriers,anticancer drugs methotrexate,6-mercaptopurine and antituberculosis drugs isoniazid and pyrazinamide were selected as drug models.Slow release of the drug is achieved by using a method of surface modification.A combined loading study was conducted on the drugs used in combination to achieve simultaneous drug release at a clinical dose ratio.Methods: Relies on the principle of crystal engineering,we prepare metal-organic frameworks with appropriate pore diameter as drug carrier,of which the structural and physicochemical properties were characterized by single crystal X-ray diffraction(SXRD),powder X-ray diffraction(PXRD),scanning electron microscopy(SEM),infrared spectroscopy(IR)and thermogravimetric analysis(TG).In order to further improved the sustained drug release performance,we improve the stability of the crystal through physical modification,and the drug release process was tracked and measured by using high performance liquid chromatograph(HPLC)and ultraviolet spectrophotometer(Uv-vis).Results: In this paper,ZIF-8 was selected as the drug carrier,and the drug was loaded by one-pot method.Chitosan was used to modify the surface of drug@ZIF-8,and the drug release time of 6-Mercaptopurine was extended to 120 hours.The drug loads of methotrexate and 6-mercaptopurine were 108.7 mg/g and 67.2 mg/g,respectively.After surface modification,the drug load of ZIF-8-methotrexate@chitosan and ZIF-8-6-mercaptopurine@chitosan ware about 199.0 mg/g and 218.0 mg/g,respectively.In addition,the combined drug methotrexate and allopurinol were successfully loaded by one-pot method with a total drug load of 219.5mg/g,the simultaneous release of the two drugs was achieved.In addition,we synthesized Zn-BTC by solvothermal method,and the synergistic antituberculosis drugs isoniazid and pyrazinamide were successfully loaded into Zn-BTC by immersed with a total drug loading of 117.3 mg/g,and the simultaneous release of synergistic drugs was also achieved.Conclusion: In this paper,the release time of anti-tumor drugs was greatly extended by post-synthesis modification,and the research results can provide basic research for the sustained release application of antitumor drugs.One-pot method was used to successfully load the drugs used in combination,and an intelligent drug loading system was obtained.Finally,synergistic anti-tuberculosis drugs ware successfully loaded into crystal by immersed,which not only reduced the emergence of tolerance,but also improved the compliance of patients.The research work in this paper provides available reference for the application of metal-organic frameworks as new drug carriers. |
