Abstract: OBJECTIVE To prepare a new ZSM-5 microporous molecular sieve based drug loaded composite and to investigate its drug release behavior in vitro. METHODS Using ZSM-5 microporous molecular sieve as carrier, a small molecule antitumor drug 5-fluorouracil(5-FU) was loaded into the molecular sieve by impregnation centrifugation and the primary drug assembly of 5-FU@ZSM-5 was prepared. Then, the surface of the primary drug assembly was coated with natural organic polymer sodium alginate(ALG) through calcification by lifting method, and the drug loaded complex of 5-FU@ZSM-5@ CaALG was finally obtained. The drug loading rate of the drug loaded complex was investigated by UV spectrophotometry. The structure and physicochemical properties were characterized by X-ray diffraction, solid UV-VIS diffuse reflectance spectroscopy, nitrogen isothermal adsorption and desorption, scanning electron microscopy and Fourier transform infrared spectroscopy. The drug release performance of 5-FU@ZSM-5@CaALG was investigated by in vitro release degree experiment. RESULTS The results of UV quantitative analysis showed that the drug loading rate of the drug loaded complex was 11.7%. The characterization results showed that the small molecule drug 5-FU entered the ZSM-5 channel and did not destroy the MFI topology of ZSM-5 after drug loading. In vitro “time-dissolution medium transformation” release experiment showed that, compared with the drug assembly of 5-FU@ZSM-5, the drug loaded complex of 5-FU@ZSM-5@CaALG showed significant pH-time dual-dependent behavior. The cumulative release rate of the drug in the artificial gastric juice within 2 h was less than 10%, that is, more than 90% of the drug could enter the artificial intestinal juice. The cumulative release rate was 85.2% in artificial gastrointestinal fluid within 48 h. CONCLUSION Microporous ZSM-5 molecular sieve can be used as an excellent carrier material for 5-FU. In combination with CaALG, it can simultaneously achieve intestinal targeted drug delivery and long-term effect.