Abstract
The molecular surface imprinted graft copolymer of chitosan with methyl methacrylate (MIP-CS-g-PMMA) were prepared by free radical polymerization with 5-fluorouracil (5-FU) as the template molecule using initiator of ammonium persulfate as adsorption system. MIPs were characterized by FTIR, X-ray diffraction, thermo-gravimetric analysis, 1H NMR and SEM. The mechanism of graft copolymerization and factors affected graft reaction were studied in details, and the optimum reaction conditions (to the highest %G and %E as the standard) were obtained at [MMA] 1.2 mol/L, [Chitosan] 16.67 mol/L, [initiator] 0.0062 mol/L, temperature 60 °C and reaction time 7 h. MIPs exhibited high recognition selectivity and excellent combining affinity to template molecular. The in vitro release of the 5-FU was highly pH-dependent and time delayed. The release behavior showed that the drugs did not release in simulated gastric fluid (pH = 1.0), and the drug release was small in the simulated small intestinal fluid (pH = 6.8), and drug abrupt release will be produced in the simulated colon fluid (pH = 7.4), indicating excellent colon-specific drug delivery behavior.
Highlights
Few studies have been reported on the preparation of MIPs with chitosan grafted poly, and no study has been reported about the pH-sensitive properties of molecular recognition
In order to overcome above shortcomings of 5-FU, and improve the chemotherapy efficiency of colorectal cancer, many groups[24,25] have focused on the development of oral colon-specific 5-FU delivery system which can avoid releasing of the oral 5-FU in the stomach and in the front of the small intestine, and can transfer the drug to release at the site of colon to increase the local concentration of the drug in the lesion
The graft copolymerization of chitosan was prepared with the initiator of ammonium persulfate
Summary
The molecular surface imprinted graft copolymer of chitosan with methyl methacrylate (MIP-CSg-PMMA) were prepared by free radical polymerization with 5-fluorouracil (5-FU) as the template molecule using initiator of ammonium persulfate as adsorption system. In order to overcome above shortcomings of 5-FU, and improve the chemotherapy efficiency of colorectal cancer, many groups[24,25] have focused on the development of oral colon-specific 5-FU delivery system which can avoid releasing of the oral 5-FU in the stomach and in the front of the small intestine, and can transfer the drug to release at the site of colon to increase the local concentration of the drug in the lesion. Based on the persulfate initiating the surface graft polymerization, we design and prepare a new oral colon-specific 5-FU delivery system with molecular surface imprinted technique with CS-PMMA as matrix microspheres and with the 5-FU as template molecule, which is the combination of the pH-development and time-delayed release mechanisms. The oral colon-specific 5-FU delivery system will be hoped to apply for treatment of colon and colorectal cancer with high efficacy and safety
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