Molecular imprinting technology has been widely studied in the field of medicine.In order to solve the problem that 5-FU is easily metabolized and released quickly,and it is toxic to hematology,neurology,cardiology,gastrointestinal tract and dermatology,aiming at the outstanding problems and shortcomings in the preparation,structure and performance regulation of traditional imprinting materials,this paper constructs a molecularly imprinted polymer(MIP)with good sustained release performance through inorganic/organic hybrid compounding.In this paper,four molecularly imprinted polymers(MIPs(PAM),MIPs(PMMA),MIPs(PAM-PMMA),ATP@GO/MIPs(PAM-PMMA))were synthesized by precipitation polymerization using the natural mineral graptolite(ATP)as a substrate,one or two of acrylamide(AM)and methyl methacrylate(MMA)as functional monomers,ethylene glycol dimethacrylate(EGDMA)as a cross-linker,and azoisobutyronitrile(AIBN)as an initiator.The effects of different functional monomers and double functional monomers as well as the incorporation of graphene on the drug release properties of 5-FU were investigatedThe different MIPs were systematically characterized by X-ray diffraction(XRD),field emission scanning electron microscopy(FESEM),high-resolution transmission microscopy(HRTEM),Fourier transform infrared spectroscopy(FT-IR)and thermogravimetry(TG).The results showed that MIPs had an irregular spherical morphology and a wrinkled surface.After eluting with the eluent,the surface of MIPs was rough and the polymer network structure was obvious.Infrared analysis showed that ATP was successfully polymerized with AM and MMA,and the addition of template molecules affected the structure of MIPs.The adsorption capacity and in vitro release of MIPs on 5-FU were investigated.The selectivity of ATP@GO/MIPs(PAM-PMMA)was investigated using three pyrimidine analogs.The toxicity of 5-FU-loaded MIPs(PAM-PMMA)and ATP@GO/MIPs(PAM-PMMA)on He La cells was also examined.The adsorption results showed that the maximum drug loading of MIPs(PMMA)and MIPs(PAM)for5-FU were both 1.6 mg/g,and the adsorption of 5-FU was consistent with the Freundlich model,which is in conformity with the pseudo first-order kinetic adsorption model.The maximum loading of 5-FU by MIPs(PAM-PMMA)and ATP@GO/MIPs(PAM-PMMA)was 12 mg/g and 2.4 mg/g,respectively,and the adsorption mode of 5-FU was consistent with the Freundlich model,which conformity with the pseudo second-order kinetic adsorption model.In addition,the adsorption capacity of MIPs(PAM-PMMA)for 5-FU increased with the increase of ATP dosage,and the maximum drug loading capacity of 12 mg/g was reached at the initial concentration of 100 mg/L of 5-FU at 0.2 g of ATP and 240 min of adsorption time.The results showed that the double functional monomer could improve the drug loading,and in addition the drug loading increased with the increase of ATP dosage.In vitro release results showed that MIPs(PMMA)reached a maximum cumulative release ratio of 70 % near 700 min,MIPs(PAM)reached a maximum cumulative release ratio of 65 % at 1000 min,MIPs(PAM-PMMA)reached 80 % at240 min,and ATP@GO/MIPs(PAM-PMMA)reached 75 % at 2000 min.It can be seen that single functional monomer MIPs(PMMA)have better slow-release effect than MIPs(PAM),and two functional monomer ATP@GO/MIPs(PAM-PMMA)have better slow-release effect than MIPs(PAM-PMMA),indicating that MIPs synthesized with GO-modified ATP as the substrate are better at reducing the release rate of 5-FU.In addition,selective adsorption showed that ATP@GO/MIPs(PAM-PMMA)had better recognition of 5-FU and specific adsorption ability to template molecules.The cytotoxicity analysis showed that the activity of He La cells decreased with increasing concentration of MIPs(PAM-PMMA)and ATP@GO/MIPs(PAM-PMMA)and time,and the maximum inhibition of cells could reach 25 % and 20 % at a concentration of100 μg/m L and a cell growth time of 72 h,respectively.All results suggest that MIPs synthesized with ATP as the substrate AM and MMA as the functional monomer can be used as a drug delivery system for 5-FU. |