探討Sulfobetaine高分子的水合性質及分子間之作用力與其在生物相容性方面之研究; Effect of the Hydration Properties and Molecular Interaction of Sulfobetaine Polymer on Its Biocompatibility

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题名:	探討Sulfobetaine高分子的水合性質及分子間之作用力與其在生物相容性方面之研究;Effect of the Hydration Properties and Molecular Interaction of Sulfobetaine Polymer on Its Biocompatibility
作者:	蔡孟甫;Meng-fu Tsai
贡献者:	化學工程與材料工程研究所
关键词:	Sulfobetaine高分子;水合能力;分子交互作用力;生物相容性;hydration property;molecular interaction;biocompatibility;Sulfobetaine polymer
日期:	2010-07-30
上传时间:	2010-12-08 13:37:39 (UTC+8)
出版者:	國立中央大學
摘要:	由於雙離子性的sulfobetaine methacrylate高分子具有良好的抗血小板或抗血漿蛋白質貼附的能力，因此很有潛力成為一個具備良好生物相容性的高分子生醫材料。然而許多研究指出材料本身與水的作用性質或水合作用和生物相容性息息相關，因此本研究選用了不同分子量(5~300kDa)的高分子聚合物poly(sulfobetaine methacrylate) PSBMA來進行水合作用的量測與分析，進一步的了解其與生物相容性的關聯性。為了了解PSBMA與水的作用性質，本研究選用不同分子量的PSBMA，利用動態濕氣吸附分析儀(DVS)、動態雷射散射粒徑分佈儀(DLS)和恆溫滴定微卡計(ITC)來量測PSBMA與水的作用性質，期待能以以上實驗之結果與不同分子量PSBMA生物相容性之關係做出說明。藉由DVS來量測PSBMA在不同溼度下的吸脫水行為。結果顯示，隨著PSBMA分子量的增加，吸脫水速率下降，推測隨著分子鏈逐漸增長而造成自身分子鏈聚集摺疊，使得水分子不易與PSBMA分子鏈上的親水基團作用。然而在分子量為23 kDa時，其吸脫水速率卻介於小分子量(10kDa、37kDa)和大分子量(60kDa~300kDa)之間。我們也利用動態雷射散射粒徑分佈儀和恆溫滴定微卡計來探討PSBMA於水溶液中分子間的作用力。結果顯示，小分子量(除了23kDa、25kDa)和大分子量PSBMA在溶液中水力半徑隨著溫度增加都有明顯降低的趨勢，而23kDa和25kDa的PSBMA溶於水中在DLS實驗的溫度範圍內都沒有觀察到明顯的水力半徑變化的情形。而由ITC實驗進行高分子溶液稀釋焓之量測，發現分子量在兩萬附近的PSBMA相較於其他分子量的PSBMA具有吸熱量較多的稀釋焓。綜合以上DVS、DLS和ITC實驗，推論隨著PSBMA分子量的增加，PSBMA在溶液中從分子間(interchain)作用力逐漸轉變為分子內(intrachain)與分子間皆具之作用力。而PSBMA分子量在兩萬左右時，PSBMA在溶液中自身分子內吸引力轉強，其溶於水時和溶液中水分子之間的作用力較接近dipole-dipole的弱作用力，分子鏈與水形成的水合基團較少，PSBMA溶於水時所需結合的水分子較少，較不易影響到溶液中水分子間的氫鍵鍵結，高分子與水分子的作用力較接近水分子與水分子間的作用力。而從溶血和凝血實驗結果可以發現，分子量在兩萬左右的PSBMA對人類紅血球的破壞程度較低以及可以延長凝血時間，展現出較佳的血液相容性。綜合材料水合性質與其生物相容性的實驗結果，本研究之結論對高分子材料生物相容性之定性的描述可為若是高分子材料能溶於水中，且較不易影響到溶液中水分子間的氫鍵鍵結，而高分子與水分子的作用力若能接近水分子與水分子間的作用力，此高分子材料就能擁有較良好的生物相容性。更深入的研究需進一步利用不同高分子材料與其他能進一步量測水分子於材料之性質之儀器設備才足以能有更完整之說明。 The zwitterionic poly(sulfobetaine methacrylate) (PSBMA) has potential to be a good biomaterial owing to high biocompatibility arisen from its adhesion resistances for platelet or plasma proteins from previous researches. In this study, the hydration behaviors of different molecular weights of zwitterionic PSBMA were investigated and the correlation between hydration behaviors of the polymers and its biocompatibility was further examined. In this study, the hydration kinetics and affinity of different molecular weights of zwitterionic PSBMA were investigated by dynamic vapor sorption (DVS). The results indicated that the hydration and dehydration rates decrease as molecular weight increases. We inferred that with the increasing of PSBMA molecular weight, polymer aggregation made water difficult to interact with the hydrophilic groups of the polymer chain. However, the hydration and dehydration rates of 23 kDa PSBMA were slower because of stronger intrachain interaction compared with other low molecular weights(10、37kDa) PSBMA. The molecular interaction of different molecular weights PSBMA in aqueous solution was investigated by dynamic light scattering (DLS) and isothermal titration calorimetry (ITC). The results showed that the hydrodynamic radius of PSBMA decrease with increased temperature. However, the hydrodynamic radius of PSBMA near 20kDa did not show obviously change at the temperature range of DLS experiment. Furthermore, the molecular weight of PSBMA near 20kDa showed higher dilution heat than those of other polymers in ITC experiment. Combined the results of DVS、DLS and ITC experiments, we inferred that with the increasing of PSBMA molecular weight, the interchain interactions turned into intrachain interactions in aqueous PSBMA solution. When the molecular weight of PSBMA near 20kDa, the stronger intrachain interaction compared with other low molecular weights(10、37kDa) PSBMA made a few water molecules interact with the polymer chain. Therefore, the few bounded water molecules in polymer are needed as PSBMA solved in aqueous solution, PSBMA polymer had a very small effect on the structure of the hydrogen-bonded network of water molecules in aqueous solution. This study also investigated the anticoagulant activity and the antihemolytic activity tests of different molecular weight of PSBMA. PSBMA performed higher blood compatibility when molecular weight near 20kDa. Compared with the hydration properties and biocompatibility of PSBMA, we inferred that if polymer had smaller effect on the structure of the hydrogen-bonded network of water molecules in aqueous solution, it seemed to give biocompatibility to the polymer.
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