- 學位論文
異丙基烯醯胺與磺基甜菜鹼共聚水凝膠之製備與性質研究及其於藥物控制釋放之行為
Preparation and Properties of Poly(N-isopropylacrylamide-co- sulfobetaine methacrylate) Hydrogels for Swelling-Controlled Drug Delivery Applications
摘要
本實驗的水膠製備是利用自由基聚合法之方式合成，選用具溫度敏感性之單體-異丙基烯醯胺(N-isopropylacrylamide，NIPAAm)與雙離子性之單體-硫代甜菜鹼 (sulfobetaine methacrylate，SBMA)，交聯劑為N,N''-methylene-bis-acrylamide，製備了三種NIPAAm/SBMA之共聚水膠並控制總單體濃度為10 wt %，其中單體之莫耳比分別為95:5，90:10與 80:20 mol %。此外，我們也製備了未含SBMA組成的非離子性水膠poly(NIPAAm)來當作一對照組。藉此探討水膠內NIPAAm與SBMA之單體組成在不同溫度下的膨潤機制與溶脹時蛋白質之釋放行為。 由作用力參數χ計算的結果顯示：隨著溫度的增加，會造成水膠與水分子間的交互作用力變弱，然而當SBMA組成的添加能提高水膠與溶劑間的交互作用力。藉由焓貢獻χH與熵貢獻χS之作用力參數可進一步得到水膠的混合焓(?H)與混合熵(?S)。我們發現溫度從25℃升至45℃時，poly(NIPAAm)具有相較於poly(NIPAAm-co-SBMA)水膠較大之亂度減少趨勢。而從χ值與亂度的結果可以得知高分子鏈之疏水性變強，使得鏈周圍形成許多有序排列的水分子，因而造成水膠在高溫之膨潤程度變小。 動態膨潤實驗的結果發現，poly(NIPAAm)水膠是以非費克擴散的方式進行溶脹；當SBMA組成的添加能提升凝膠高分子鏈鬆弛的速率，使得溶脹機制轉變為費克擴散的行為，使得水分子可以較快速進入水膠內而膨潤開來。 最後，進一步的分析水膠膨潤機制對於溶脹時蛋白質lysozyme與BSA在不同溫度下釋放的影響。結果顯示SBMA的添加有助於蛋白質在37℃下於poly(NIPAAm-co-SBMA)水膠的釋放，且釋放機制由溶脹控制轉變為擴散控制的方式進行。
並列摘要
A series of copolymeric hydrogels based on N-isopropylacrylamide (NIPAAm), zwitterionic sulfobetaine methacrylate (SBMA) were prepared by free radical polymerization in this study. N,N''-methylene -bis-acrylamide (NMBA) as a crosslinker, we prepared three types of poly(NIPAAm-co-SBMA) copolymeric hydrogels and controlled the total monomer concentration was 10 wt%, which the monomer molar ratio were 95:5, 90:10 and 80:20 mol%, respectively. In addition, we also prepared a poly(NIPAAm) hydrogel as a control to investigate the swelling mechanism and the release of protein in the swelling from hydrogels in various compositions and temperatures. The results of the interaction parameter χ calculated showed that the presence of the SBMA composition decreases the interaction parameter because of the increasing interaction between hydrogel networks and water. Enthalpy change (?H) and entropy change (?S) were obtained by χ H and χ S . They were both negative, and their absolute values increased with the temperature; this meant that the number of ordered water increased with decreasing total water content at elevated temperature. Furthermore, the phenomenon was more obvious for p(NIPAAm) gel than for p(NIPAAm/SBMA) gels because of the greater hydrophobicity of p(NIPAAm). In the dynamic swelling experiment, we have attempted to investigate the effect of composition and temperature on the swelling mechanism of NIPAAm containing SBMA hydrogels. The results revealed that the content of SBMA in poly(NIPAAm) hydrogels would facilitate the increase of relaxation rate and diffusion coefficient of water entering the hydrogels. Furthermore, the presented copolymeric hydrogels are investigated for using in protein release. The results were observed that the addition of SBMA in hydrogel could increase the releasing of protein in hydrogels at 37 ℃. And the releasing of protein increase with the amount of SBMA increase in hydrogel.With increasing the content of SBMA in p(NIPAAm) hydrogel, it would facilitate the behavior of protein release. And the mechanism of release would transfer from relaxation-controlled process to diffusion-controlled process.
參考文獻
延伸閱讀
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