海藻酸為具pH敏感性之天然高分子，而聚麩胺酸亦具有相當好的親水性和pH敏感性且在人體中本就存在，本論文利用鈣型聚麩胺酸(Ca2+-γ-PGA)作為離子交鏈劑，與海藻酸鈉進行交鏈，製出與一般使用氯化鈣交聯成膜不同的水凝膠。
本論文中針對不同比例組成水膠在不同pH值的環境測試其膨潤性質，另外也加入傳統的海藻酸-氯化鈣水膠進行比較，藉由壓縮模數(G)來計算交聯密度，接下來，將合成出的水膠浸泡於維他命C醣苷(AA2G)當中，並觀察其釋放機制。
實驗結果顯示海藻酸-聚麩胺酸水膠在各性質上均優於海藻酸-氯化鈣水膠與海藻酸-鹽酸水膠，並仍具有pH敏感性而且其壓縮模數跟交聯密度均相對較小，表示膜的剛性較小，韌性較大，在釋放行為方面，釋放速率很快，在10分鐘至一小時內隨即達到最大釋放量，而且隨著海藻酸鈉濃度增加，釋放出來的濃度隨之增加，釋放比率也逐漸上升。

Alginate is a pH-sensitive natural polymer, and PGA is a hydrophilic natural polymer also with good pH-sensitivity. In this study, we successfully cross-linked alginate and calcium form γ-polyglutamic acid, as an ion cross-linking agent, to prepare a novel hydrogel instead of calcium chloride.
The resulting hydrogels were tested about their swelling ratio in different pH conditions and different alginate contains, and they also compared with the traditional hydrogels cross-linking with calcium chloride. Then, effective cross-linking density (νe) of hydrogel was characterized according to the value of compression modulus (G). Afterwards, these hydrogels were soaked in aqueous solution of AA2G, and the releasing behavior would be observed.
The results show that this hydrogel is much better than alginate- calcium chloride hydrogel, and it still exhibits pH-sensitivity. The value of compression modulus and effective cross-linking density of hydrogels is smaller, hence the toughness is bigger. The releasing rate is fast, however, the releasing concentration increased with the concentration of alginate.

[1] Wichterle O, Lím D.Hydrophilic gels for biological use. Nature 1960; 185: 117-118
[2] Perera IK, Perkins J, Kantartzoglou Spin-coated samples for high resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of large proteins. Rapid Communications in Mass Spectrometry 1995; 9: 180-187
[3] Kopeček J.Smart and genetically engineered biomaterials and drug delivery systems. European Journal of Pharmaceutical Sciences 2003; 20: 1–16
[4] Langer RS, Peppas NA.Present and future applications of biomaterials in controlled drug delivery systems. Biomaterials 1981; 2: 201-214
[5] Hoffman AS.Present and emerging applications of polymeric biomaterials. Clinical Materials 1992; 11: 13-18
[6] Ghandehari H, Cappello J. Genetic engineering of protein-based polymers: potential in controlled drug delivery. Pharmaceutical Research 1998; 15: 813-815
[7] Nagarsekar A, Crissman J, Crissman M, Ferrari F, Cappello J, Ghandehari H.Genetic engineering of stimuli-sensitive silkelastin-like protein block copolymers. Biomacromolecules 2003; 4: 602-607

[8] Sugiura S, Oda T, Izumida Y, Aoyagi Y, Satake M, Ochiai A, Ohkohchi N, Nakajima M. Size control of calcium alginate beads containing living cells using micro-nozzle array. Biomaterials 2005; 26: 3327-3331
[9] Ougizawa T, Inoue T.UCST and LCST Behavior in Polymer Blends and Its Thermodynamic Interpretation. Polymer Journal 1986; 18: 521-527
[10] Bae YH, Okano T, Kim SW.Temperature dependence of swelling of crosslinked poly(N,N -alkyl substituted acrylamides) in water. Journal of Polymer Science, Part B: Polymer Physics 1990; 28: 923-936
[11] Freitas RFS, Cussler EL.Temperature sensitive gels as extraction solvents. Chemical Engineering Science 1987; 42: 97-103
[12]葉明熙, “水膠之生醫應用技術”, 化工資訊與商情期刊, 2004, 13: 42-47
[13] Soppimath KS, Kulkarni AR, Aminabhavi TM.Chemically modified polyacrylamide-g-guar gum-based crosslinked anionic microgels as pH-sensitive drug delivery systems: preparation and characterization. Journal of Controlled Release 2001; 75: 331-345
[14] González NC, Kellaway IW, Fuente HB, Igea SA, Charro BD, Espinar FJO, Méndez JB. Design and evaluation of buccoadhesive metoclopramide hydrogels composed of poly(acrylic acid) crosslinked with sucrose. International Journal of Pharmaceutics 1993; 100: 65-70
[15] Anderson BC, Bloom PD, Sheares VV, Mallapragada SK.Synthesis and characterization of water soluble block copolymers for pH-sensitive delivery. Materials Research Society Symposium - Proceedings 2001; 662: 181-186
[16] Albin G, Horbett TA, Ratner BD.Glucose sensitive membranes for controlled delivery of insulin: Insulin transport studies. Journal of Controlled Release 1985; 2: 153-164
[17] Barnes C,D'Silva C, Jones JP, Lewis TJ.A concanavalin A-coated piezoelectric crystal biosensor. Sensors and Actuators B: Chemical 1991; 3: 295-304
[18] Qiu Y, Park K.Environment-sensitive hydrogels for drug delivery. Advanced Drug Delivery Reviews 2001; 53: 321-339
[19] Kitano S, Koyama Y, Kataoka K, Okano T, Sakurai Y.A novel drug delivery system utilizing a glucose responsive polymer complex between poly (vinyl alcohol) and poly (N-vinyl-2-pyrrolidone) with a phenylboronic acid moiety. Journal of Controlled Release 1992; 19: 161-170
[20] Kiser PF, Wilson G, Needham D.A synthetic mimic of the secretory granule for drug delivery. Nature 1998; 394: 459-462
[21] Murdan S.Electro-responsive drug delivery from hydrogels. Journal of Controlled Release 2003; 92: 1-17
[22] Beebe DJ, Moore JS, Bauer JM, Yu Q, Liu RH, Devadoss C, Jo BH.Functional hydrogel structures for autonomous flow control inside microfluidic channels. Nature 2000; 404: 588-590
[23] Heilmann SM, Smith II HK.Acrylic-functional aminocarboxylic acids and derivatives as components of pressure-sensitive adhesives. Journal of Applied Polymer Science 1979; 24: 1551-1564
[24] Miyata T, Asami N, Uragami T.A reversibly antigen-responsive hydrogel. Nature 1999; 399: 766-769
[25] Eichenbaum G.M, Kiser PF, Simon SA, Needham D.pH and ion-triggered volume response of anionic hydrogel microspheres. Macromolecules 1998; 31: 5084-5093
[26] Sutton A.Reduction of strontium absorption in man by the addition of alginate to the diet. Nature 1967; 216: 1005-1007
[27] Hesp R, Ramsbottom B.Effect of sodium alginate in inhibiting uptake of radiostrontium by the human body. Nature 1965, 208: 1341-1342
[28] Schweiger RG.Acetylation of alginic acid. II. Reaction of algin acetates with calcium and other divalent ions. Journal of Organic Chemistry 1962, 27: 1789-1791
[29] French D., Himmelstein K. and Mauger J. M., “Physicochemical aspects of controlled release of substituted benzoic and naphthoic acids from carbopol gels”, J. Contr. Rel. 1995, 37: 281
[30] Peppas N. A., Moynihah H. J. and Lucy M. L., “The structure of highly crosslinked poly (2-hydroxyethyl methacrylate) hydrogel”, J. Biomed. Mat. Res.1985, 19:397
[31] Drurya J. L., Dennisb R. G., Mooneya D. J., “The tensile properties of alginate hydrogels”, Biomaterials. 2004, 25:3187–3199
[32] Rees DA.Polysaccharide shapes and their interactions— Drug encapsulation in some recent advances. Pure and Applied. Chemistry. 1981, 53: 1–14.
[33] Serp D, Mueller M, Stockar UV, Marison IW.Low-temperature electron microscopy for the study of polysaccharide ultrastructures in hydrogels. II. Effect of temperature on the structure of Ca2+-alginate beads. Biotechnology and Bioengineering 2002; 79: 253-259
[34] Gilchrist T, Martin AM.Wound treatment with Sorbsan — an alginate fibre dressing. Biomaterials 1983, 4: 317-320
[35] Chan LH, Heng PWS.Effects of aldehydes and methods of cross-linking on properties of calcium alginate microspheres prepared by emulsification. Biomaterials 2002, 23: 1319-1326
[36] Mumper RJ, Huffman AS, Puolakkainen PA, Bouchard LS, Gombotz WR.Calcium-alginate beads for the oral delivery of transforming growth factor-β1 (TGF-β1): stabilization of TGF-β1 by the addition of polyacrylic acid within acid-treated beads. Journal of Controlled Release 1994; 30: 241-251
[37] Gudmund Skj»k-Bræk, Hans Grasdalen and Bjørn Larsen.Monomer sequence and acetylation pattern in some bacterial alginates. Carbohydrate Research 1986; 154: 239-250
[38] Scheurich P, Schnabl H, Zimmermann U,Klein J.Immobilisation and mechanical, support of individual protoplasts. Biochimica et biophysica acta 1980; 598: 645-651
[39]Kikuchi A, Kawabuchi M, Sugihara M, Sakurai Y, Okano T.Pulsed dextran release from calcium-alginate gel beads. Journal of Controlled Release 1997; 47: 21-29
[40]Amsden B, Turner N.Diffusion characteristics of calcium alginate gels. Biotechnology and Bioengineering 1999; 65: 605-610
[41] Nagasawa M, Holtzer A.The Helix-Coil Transition in Solutions of Polyglutamic Acid. Journal of the American Chemical Society; 86: 538-543
[42] 楊國明,”藥物釋放之親疏水性乙基纖維素/羫丙基纖維素掺合微粒的製備與其藥物釋放之研究”, 成功大學化學工程研究所博士論文, 2006
[43]蕭伊妙, “維他命C醣苷和熊果素對於B16黑色素瘤細胞抑制黑色素生成之研究”, 清華大學化學工程研究所碩士論文, 2006
[44]許芳菁, “海藻酸-聚麩胺酸水膠應用於創傷敷料之評估”,國立台灣科技大學高分子工程所碩士論文,2007
[45] Lin YH, Liang HF, Chung CK, Chen MC, Sung HW. Physically crosslinked alginate/N,O-carboxymethyl chitosan hydrogels with calcium for oral delivery of protein drugs. Biomaterials 2005; 26: 2105-2113
[46]Wang SC, Chen BH, Wang LF, Chen JS. Characterization of chondroitin sulfate and its interpenetrating polymer network hydrogels for sustained-drug release. J. of Pharmaceutics 2007; 329:103–109
[47] Moe ST, Elgsaeter A, Bræk GS, Smidsrød O.A new approach for estimating the crosslink density of covalently crosslinked ionic polysaccharide gels. Carbohydrate Polymers 1993; 20: 263-268