Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara, Turkey.
Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara, Turkey.
Colloids Surf B Biointerfaces. 2015 Feb 1;126:401-6. doi: 10.1016/j.colsurfb.2014.12.038. Epub 2015 Jan 3.
The objective of this study is to prepare imprinted cryogel discs for delivery of 5-fluorouracil. The coordinate bond interactions are utilized to accomplish a coordination complex between metal-chelate monomer N-methacryloyl-L-histidine and 5-FU with the assistance of Cu(2+) ion. The complex is copolymerized with hydroxyethyl methacrylate to produce poly(hydroxyethyl methacrylate-N-methacryloyl-(L)-histidine methyl ester) cryogel discs. The cryogel discs are characterized thoroughly by performing swelling tests, scanning electron microscopy, differential scanning calorimetry and X-ray diffraction studies. In vitro delivery studies are performed to investigate the effects of cross-linker ratio, medium pH and drug concentration. 5-FU imprinted cryogel discs have highly macroporous structures. Drug molecules are homogeneously dispersed in the 5-FU imprinted cryogel matrix. The cumulative release of 5-FU decreased by increasing the cross-linker density in the polymer matrix. Delivery rate of 5-FU varied with different pH values in a coordination complex since metal ion acts as a Lewis acid, and the ligand, i.e. 5-FU acts as a Lewis base. The cumulative release of 5-FU increased with increasing drug concentration in polymer matrix. The nature of the 5-FU transport mechanism is non-Fickian.
本研究的目的是制备用于递送 5-氟尿嘧啶的印迹 cryogel 盘。利用配位键相互作用，在 Cu(2+)离子的协助下，实现金属螯合单体 N-丙烯酰基-L-组氨酸与 5-FU 之间的配位络合物。该络合物与羟乙基甲基丙烯酸酯共聚，生成聚（羟乙基甲基丙烯酸酯-N-丙烯酰基-（L）-组氨酸甲酯）cryogel 盘。通过进行溶胀试验、扫描电子显微镜、差示扫描量热法和 X 射线衍射研究，对 cryogel 盘进行了全面的表征。进行体外释放研究以考察交联剂比、介质 pH 值和药物浓度的影响。5-FU 印迹 cryogel 盘具有高度的大孔结构。药物分子均匀分散在 5-FU 印迹 cryogel 基质中。随着聚合物基质中交联剂密度的增加，5-FU 的累积释放量减少。由于金属离子作为路易斯酸，配体即 5-FU 作为路易斯碱，因此在配位络合物中，5-FU 的释放速率随不同的 pH 值而变化。随着聚合物基质中药物浓度的增加，5-FU 的累积释放量增加。5-FU 运输机制的性质是非菲克定律。
