大分子印迹聚乙烯基吡咯烷酮基/海藻酸钙聚合物微球的研究
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摘要
本文以海藻酸钠和聚乙烯基吡咯烷酮为原料,采用反相悬浮钙离子交联的方法,分别设计和制备了粒径约为200-300μm的聚乙烯基吡咯烷酮/海藻酸钙(PVP/CA)、水解聚乙烯基吡咯烷酮/海藻酸钙(CHPVP/CA)聚合物微球。用光学显微镜观测了微球的形貌,并讨论了影响微球粒径大小、分布和形态的各种因素:分散剂的种类及用量、水油比、搅拌速度以及单独影响CHPVP/CA聚合物微球的HPVP的水解度等。用紫外分光光度计和电导率仪等分析微球的重结合行为。探讨了各种操作手段如洗脱过程、洗脱时间等对微球的重结合量和印迹效率的影响,以及外部条件如交联剂CaCl2的浓度、BSA溶液pH值、离子强度(NaCl和CaCl2)等的影响。
重结合热力学和动力学表明,两种印迹微球均比非印迹微球对目标蛋白质表现出更高的重结合量和特异性。同时发现,由于CHPVP/CA聚合物微球和PVP/CA聚合物微球交联方式上的差别,CHPVP/CA聚合物微球的互穿网络结构比PVP/CA的半互穿网络结构更加稳定和致密。CHPVP/CA聚合物基材与BSA结合的孔穴和官能团位点具有更好的特异重结合性。所以CHPVP/CA聚合物微球的稳定性和印迹效率要高于PVP/CA聚合物微球,但是重结合量却低于PVP/CA聚合物微球,而且CHPVP/CA聚合物微球的重结合效果对离子强度的敏感性要比PVP/CA高。
Calcium polyvinylpyrrolidone/alginate polymer microspheres (PVP/CA MIPMs) and calcium hydrolyzed polyvinylpyrrolidone/alginate polymer microspheres (PVP/CA MIPMs) macromolecularly imprinted hybrid polymer microspheres were firstly designed and prepared with sodium alginate (SA) and polyvinylpyrrolidone (PVP) by using CaCl2 as gelling agent in inverse-phase suspension. Morphology of BSA imprinted PVP-based hybrid polymer microspheres was observed by optical microscopy. The effect of the kind and quantity of the stabilizers, the ratio between the continuous phase and the disperse phase, the stiring speed, the percent of hydrolyzed PVP on the size, size distribution and morphology of the hybrid polymer microspheres. The rebinding capacity of the imprinted and non-imprinded microspheres is determined by UV spectrophotometry and conductivity meter. The processing methods such as eluting progress and time are inspected as impacting factors towards rebinding quantity and imprinting efficiency. The effects of extra stimulation like concentration of crosslinking agent (CaCl2), pH of the BSA solution and the ionic strength of Na+ and Ca2+ are also studied.
Rebinding dynamic and thermodynamic behaviors of the two imprinted microspheres were evaluated, resulting in a higher affinity for imprinted microspheres relative to non-imprinted ones. CHPVP/CA MIPMs possess an interpenetrating network (IPNs) that is more stable and compact than the semi-IPNs of the PVP/CA due to the difference in their crosslinking manners. The cavities and functional sites of CHPVP/CA MIPMs are more facilitate in the specific rebinding process. Higher stability and imprinting efficiency are found in CHPVP/CA MIPMs rather than in the PVP/CA MIPMs, however the rebinding quantity is lower than the latter. Meanwhile, the rebinding behavior of the CHPVP/CA MIPMs is more sensitive to ionic strength than PVP/CA MIPMs.
重结合热力学和动力学表明,两种印迹微球均比非印迹微球对目标蛋白质表现出更高的重结合量和特异性。同时发现,由于CHPVP/CA聚合物微球和PVP/CA聚合物微球交联方式上的差别,CHPVP/CA聚合物微球的互穿网络结构比PVP/CA的半互穿网络结构更加稳定和致密。CHPVP/CA聚合物基材与BSA结合的孔穴和官能团位点具有更好的特异重结合性。所以CHPVP/CA聚合物微球的稳定性和印迹效率要高于PVP/CA聚合物微球,但是重结合量却低于PVP/CA聚合物微球,而且CHPVP/CA聚合物微球的重结合效果对离子强度的敏感性要比PVP/CA高。
Calcium polyvinylpyrrolidone/alginate polymer microspheres (PVP/CA MIPMs) and calcium hydrolyzed polyvinylpyrrolidone/alginate polymer microspheres (PVP/CA MIPMs) macromolecularly imprinted hybrid polymer microspheres were firstly designed and prepared with sodium alginate (SA) and polyvinylpyrrolidone (PVP) by using CaCl2 as gelling agent in inverse-phase suspension. Morphology of BSA imprinted PVP-based hybrid polymer microspheres was observed by optical microscopy. The effect of the kind and quantity of the stabilizers, the ratio between the continuous phase and the disperse phase, the stiring speed, the percent of hydrolyzed PVP on the size, size distribution and morphology of the hybrid polymer microspheres. The rebinding capacity of the imprinted and non-imprinded microspheres is determined by UV spectrophotometry and conductivity meter. The processing methods such as eluting progress and time are inspected as impacting factors towards rebinding quantity and imprinting efficiency. The effects of extra stimulation like concentration of crosslinking agent (CaCl2), pH of the BSA solution and the ionic strength of Na+ and Ca2+ are also studied.
Rebinding dynamic and thermodynamic behaviors of the two imprinted microspheres were evaluated, resulting in a higher affinity for imprinted microspheres relative to non-imprinted ones. CHPVP/CA MIPMs possess an interpenetrating network (IPNs) that is more stable and compact than the semi-IPNs of the PVP/CA due to the difference in their crosslinking manners. The cavities and functional sites of CHPVP/CA MIPMs are more facilitate in the specific rebinding process. Higher stability and imprinting efficiency are found in CHPVP/CA MIPMs rather than in the PVP/CA MIPMs, however the rebinding quantity is lower than the latter. Meanwhile, the rebinding behavior of the CHPVP/CA MIPMs is more sensitive to ionic strength than PVP/CA MIPMs.
引文
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[6] Vlatakis G, Andersson L I, Muller R, et al. Drug assay using antibody mimics made by molecular imprinting. Nature, 1993, 361(3): 645-647
[7] Huang J J, Zhao K Y, Gao N, et al. Preparation of macromolecularly imprinted calcium phosphate/alginate hybrid polymer microspheres. J Hebei University of Technology (in Chinese), 2007, 36: 21-25
[8] Wizeman, W J, Kofinas, P. Molecularly imprinted polymer hydrogels displaying isomeri -cally resolved glucose binding. Biomaterials 2001, 22:1485-91
[9] Rong F, Feng X G, Li P, et al. Preparation of molecularly imprinted microspheres by photo-grafting on supports modified with iniferter. Chin Sci Bull, 2006, 51(21): 2566-2571
[10] By Feng Shi, Zan Liu, GuangluWu, et al. Surface Imprinting in Layer-by-Layer Nanostructured Films. Adv Funct Mater, 2007, 17(11): 1821-1827
[11] Jia Niu, Feng Shi, Zan Liu, et al. Reversible Disulfide Cross-Linking in Layer-by-Layer Films: Preassembly Enhanced Loading and pH/Reductant Dually Controllable Release. Langmuir, 2007, 23(11): 6377-6384
[12] Pang X S, Cheng G X, Lu S L. Syn sis of polyacrylamide gel beads with electrostatic functional groups for the molecular imprinting of bovine serum albumin. Anal Bioanal Chem, 2006, 384(1): 225-330
[13] X. S. Pang, G. X. Cheng, R. S. Li, Y. H. Zhang, Analytica Chimica Acta 550, 2005: 13-17
[14] Parmpi P, Kofinas P. Biomimetic glucose recognition using molecularly imprinted polymer hydrogels. Biomaterials, 2004, 25:1969-73
[15] Nicholas W T, Christopher W J, Keith R B, et al. From 3D to 2D: A Review of the Molecular Imprinting of Proteins, Biotechnol Prog 2006, 22, 1474-1489
[16] Zhang F J, Cheng G X, Ying X G. Emulsion and macromolecules templated alginate basedpolymer microspheres. React Funct Polym, 2006, 66: 712-719
[17] Pang X S, Cheng G X, Zhang Y H, Lu S L. Soft-wet polyacrylamide gel beads with the imprinting of bovine serum albumin. React Funct Polym, 2006, 66, 1182-1188
[18] Ye L, Mosbach K. Molecularly imprinted microspheres as antibody binding mimics. React. Funct. Polym, 2001, 48(1-3): 149-157
[19] Cameron Alexander, Hakan S. Andersson, Lars I. Andersson, et al, Molecular imprinting science and technology: a survey of the literature for the years up to and including 2003, J. Mol. Recogni, 2006, (19): 106-180
[20] Pang X S, Cheng G X. Polymer Research Developments, New York. Nova Science Publishers Inc. 2006, 91-106
[21] Zhang L Y, Cheng G X, Fu C. Molecular selectivity of tyrosine- imprinted polymers prepared by seed swelling and suspension polymerization, Poly Int, 2002,51(8): 687-692
[22] Khotimchenko, Yu S, Koatev, V V, Savchenko, O V, et al. Physical-chemical properties, Physiological Activity, and Usage of Alginates, the Polysacarides of Brown Algae. Russian journal of marine biology, 2001, 27 (1) 53-64
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[24] Go?khan Demirel, Go?kc.en O?zc.etin, Eylem Turan, et al, pH/Temperature-Sensitive Imprinted Ionic Poly(N-tert-butylacrylamide-co-acrylamide/maleic acid) Hydrogels for Bovine Serum Albumin, Macromol. Biosci. 2005, (5): 1032-1037
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[26] Rachkov A, Minoura N. Towards molecularly imprinted polymers selective to peptides and proteins. The epitope approach, Biochimica et Biophysica Acta, 2001, 1544: 255-266
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