English
往期目录
新闻公告
More
化学进展 2008, Vol. 20 Issue (01): 126-139 前一篇   后一篇

• 综述与评论 •

海藻酸钠和壳聚糖聚电解质微胶囊及其生物医学应用*

刘袖洞1,2 于炜婷1 王为1 雄鹰1 马小军1** 袁权1   

  1. (1. 中国科学院大连化学物理研究所 大连 116023； 2. 大连大学环境与化学工程学院 大连 116622)
  • 收稿日期:2007-01-18 修回日期:2007-05-08 出版日期:2008-01-24 发布日期:2008-01-24
  • 通讯作者: 马小军
下载PDF ( 5149 ) 引用
导出

Polyelectrolyte Microcapsules Prepared by Alginate and Chitosan for Biomedical Application

Liu Xiudong1,2; Yu Weiting1; Wang Wei1; Xiong Ying1; Ma Xiaojun1** ; Yuan Quan1   

  1. (1. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; 2. College of Environment and Chemical Engineering, Dalian University, Dalian 116622, China)
  • Received:2007-01-18 Revised:2007-05-08 Online:2008-01-24 Published:2008-01-24
  • Contact: Ma Xiaojun
本文综述了天然多糖聚电解质海藻酸钠和壳聚糖的结构与化学性能（包括凝胶性能、生物相容性、生物可降解性及温和反应性）；微胶囊制备技术及其强度性能和膜渗透性评价方法；微胶囊作为细胞载体在体内分泌治疗性物质（如：胰岛素、多巴胺）或分解代谢毒性物质（如：尿素），作为三维药物筛选系统、干细胞增殖分化研究工具，以及药物释放载体等生物医学领域的研究进展；最后讨论了天然多糖微胶囊研究与应用中需要解决的问题。
关键词： 海藻酸钠, 壳聚糖, 聚电解质, 微胶囊, 细胞移植, 细胞培养, 药物输送
This review highlights the progress in the structure and chemical properties of natural polysaccharides (alginate and chitosan) including gel formation, biocompatibility, biodegradability and mild reaction ability; preparation technologies of microcapsules (Polyelectrolyte complexation/Polyelectrolyte layer-by-layer self assembly) and the evaluation methods on microcapsule mechanical and permeable properties; microcapsules entrapping cells secreting therapeutics (such as insulin and dopamine) or decomposing toxic metabolites (such as urea) in vivo, microcapsules serving as three-dimensional drug screening systems and microenvironment for the proliferation and differentiation of stem cells, microcapsules serving as the drug carriers for controlled release. Finally, the challenge and problem for the development of microcapsules are discussed.
Key words: alginate, chitosan, polyelectrolyte, microcapsule, cell transplantation, cell culture, drug delivery

中图分类号: 

()

[ 1 ] 马小军(Ma X J) 编著. 微胶囊与人工器官(Microcapsule and Artificial Organs) . 北京: 化学工业出版社(Beijing : Chemical Industry Press) , 2002
[ 2 ] Chang T M S. Science , 1964 , 146 : 524 —525
[ 3 ] Lim F , Sun A M. Science , 1980 , 210 : 908 —910
[ 4 ] 刘袖洞(Liu X D) , 何洋(He Y) , 马小军(Ma X J) 等. 科学通报(Chinese Science Bulletin) , 2000 , 45(23) : 2476 —2485
[ 5 ] Uludag H , de Vos P , Tresco P A. Adv. Drug Deliver. Rev. ,2000 , 42 : 29 —64
[ 6 ] Wang W, Liu X D , Ma X J , et al . J . Mater. Chem. , 2006 , 16 :3252 —3267
[ 7 ] Abalovich A , Jatimliansky C , Diegex E , et al . Transplant .Proceedings , 2001 , 33 : 1977 —1979
[ 8 ] Uhrich K E , Cannizzaro S M, Langer R S , et al . Chem. Rev. ,1999 , 99 : 3181 —3198
[ 9 ] Fu K, Pack D W, Langer R S , et al . Pharm. Res. , 2000 , 17 :100 —106
[10] George M, Abraham T E. J . Control . Release , 2006 , 114 : 1 —14
[11] Jen A C , Wake M C , Mikos A G. Biotechnol . Bioeng. , 1996 ,50 : 357 —364
[12] Orive G, Hernández RM, Pedraz J L , et al . Trends Biotechnol . ,2004 , 22(2) : 87 —92
[13] Smidsr?d O , Skjaok-Br·k G. Trends Biotechnol . , 1990 , 8 : 71 —78
[14] Gombotz W R , Wee S F. Adv. Drug Deliver. Rev. , 1998 , 31 :267 —285
[15] Sugawara S , Imai T , Otagiri M. Pharm. Res. , 1994 , 11 : 272 —277
[16] Draget K I , Skj?k-Br·k G, Smidsr?d O. Carbohydr. Polym. ,1994 , 25 : 31 —38
[17] Rees D A. Pure Appl . Chem. , 1981 , 53 : 1 —14
[18] 薛伟明(Xue WM) , 于炜婷( Yu W T) , 马小军(Ma X J )等. 高等学校化学学报( Chemical Journal of Chinese Universities) , 2004 , 25(7) : 1342 —1346
[19] Shoichet M S , Li R H , White ML , et al . Biotechnol . Bioeng. ,1996 , 50 : 374 —381
[20] Al-Shamkhani A , Duncan R J . J . Bioact . Compat . Polym. ,1995 , 10 : 4 —13
[21] Alsberg E , Kong HJ , Mooney J J , et al . J . Dent . Res. , 2003 ,82 : 903 —908
[22] Bystricky S , Malovikova A , Sticzay T. Carbohydr. Res. , 1990 ,13 : 283 —294
[23] Strand B L , Ryan TL , Veld P I , et al . Cell Transplant . , 2001 ,10 : 263 —275
[24] IllumL , Jabbal2Gill I , Hinchcliffe M, et al . Adv. Drug Deliver.Rev. , 2001 , 51 : 81 —96
[25] 尹承慧(Yin C H) . 国外医药———合成药、生化药、制剂分册(World Pharmacy) , 2000 , 21(2) : 106 —109
[26] IllumL. Pharm. Res. , 1998 , 15(9) : 1326 —1331
[27] Janes K A , Calvo P , Alonso M J . Adv. Drug Deliver. Rev. ,2001 , 47 : 83 —97
[28] Temel A , Kazokoglu H , Taga Y. Ann. Ophthalmol . , 1991 , 23 :191 —194
[29] Ren D W, Yi H F , Ma X J , et al . Carbohydr. Res. , 2005 ,340 : 2403 —2410
[30] Ren D W, Yi H F , Ma X J , et al . J . Membr. Sci . , 2006 , 280 :99 —107
[31] Ramdas M, Dileep K J , Anitha Y. J . Biomat . Appl . , 1999 , 13 :290 —296
[32] Bartkowiak A , Hunkeler D. Ann. N. Y. Acad. Sci . , 1999 ,875 : 36 —45
[33] Bugarski B , Li Q , Goosen M F A , et al . AIChE J . , 1994 , 40 :1026 —1031
[34] Goosen M F A , Al2Ghafri A S , El Mardi O , et al . Biotechnol .Prog. , 1997 , 13 : 497 —502
[35] 任吉伦(Ren J L) , 马小军(Ma X J ) , 何洋(He Y) . CN 00 253 538. 6
[36] Koch S , Schwinger C , Rainov N G, et al . J . Microencapsul . ,2003 , 20 (3) : 303 —316
[37] Hardikar A A , Risbud MV , Bhonde R R. J . Biosci . , 1999 , 24(3) : 371 —376
[38] Sakai S , Kawabata K, Ono T , et al . Biotechnol . Bioeng. , 2004 ,86 (2) : 168 —173
[39] Sugiura S , Oda T , Nakajima M, et al . Biomaterials , 2005 , 26(16) : 3327 —3331
[40] Lencki R W J , Neufeld R J , Spinney T. US 4 822 534 , 1989
[41] Poncelet D , Lencki R W J , Neufeld R J , et al . Appl . Microbiol .Biotechnol . , 1992 , 38 : 39 —45
[42] Poncelet D , Desmet B P , Neufeld R J , et al . Appl . Microbiol .Biotechnol . , 1995 , 43 : 644 —650
[43] Poncelet D , Babak V , Dulieu C , et al . Colloid Surface A , 1999 ,155(2/3) : 171 —176
[44] Esquisabel A , Hernandez R M, Pedraz J L. J . Microencapsul . ,1997 , 14 : 627 —638
[45] Alexakis T , Boadi D K, Quong D , et al . Appl . Biochem.Biotechnol . , 1995 , 50 : 93 —106
[46] Ribeiro A J , Neufeld R J , Arnaud P , et al . Int . J . Pharm. ,1999 , 187 : 115 —123
[47] Vandenberg G W, de La Noüe J . J . Microencapsul . , 2001 , 18 :433 —441
[48] Muramatsu N , Nakauchi K. J . Microencapsul . , 1998 , 15 (6) :715 —723
[49] Joscelyne S M, Tr? gr? dh G. J . Membr. Sci . , 2000 , 169 : 107 —117
[50] Liu X D , Bao D C , Ma X J , et al . J . Appl . Polym. Sci . , 2003 ,87 : 848 —852
[51] Yi Y Y, Kermasha S , Neufeld R J , et al . J . Mol . Catal . B-Enzym. , 2002 , 19/20 : 319 —325
[52] Moslemy P , Guiot S R , Neufeld R J . Enzyme Microb. Tech. ,2002 , 30 : 10 —18
[53] 梁振鹏(Liang Z P) , 王朝阳(Wang C Y) , 孙启龙(Sun Q L)等. 化学进展( Progress in Chemistry) , 2004 , 16 (4) : 485 —491
[54] An Z H , Tao C , Lu G, et al . Chem. Mater. , 2005 , 17 : 2514 —2519
[55] An Z H , Mêhwald H , Li J B. Biomacromolecules , 2006 , 7 :580 —585
[56] Qiu X P , Leporatti S , Donath E , et al . Langmuir , 2001 , 17 :5375 —5380
[57] Ye S Q , Wang C Y, Liu X X, et al . J . Control . Release , 2005 ,106 : 319 —328
[58] Ye S Q , Wang C Y, Liu X X, et al . J . Control . Release , 2006 ,112 : 79 —87
[59] Gao C Y, Donath E , Mêhwald H , et al . Angew. Chem. Int .Ed. , 2002 , 114 : 3789 —3793
[60] Li R H. Adv. Drug Deliver. Rev. , 1998 , 33 : 87 —109
[61] Hunkeler D , Rehor A , Ceausoglu I , et al . Ann. N. Y. Acad.Sci . , 2001 , 944 : 456 —471
[62] Jay A WL , Edwards MA. Can. J . Physiol . Pharm. , 1968 , 46 :731 —737
[63] Matthew H W, Salley S O , Peterson W D , et al . Biotechnol .Prog. , 1993 , 9 : 510 —519
[64] Zhao L , Zhang Z B. Artif . Cell Blood Substit . Immobil .Biotechnol . , 2004 , 32(1) : 25 —40
[65] Dautzenberg H , Lukanoff B , Eckert U , et al . Berichte Der Bunsen-Gesellschaft-Phys. Chem. Chem. Phys. , 1996 , 100 :1045 —1053
[66] Leblond F A , Tessier T , Halle J P. Biomaterials , 1996 , 17 :2097 —2102
[67] Lee C S , Chu I M. Artif . Organs. , 1997 , 21 : 1002 —1006
[68] Ma XJ , Vacek I , Sun A M. Artif . Cell Blood Substit . Immobil .Biotechnol . , 1994 , 22 : 43 —69
[69] 马小军(Ma X J) , 解玉冰(Xie Y B) , 周丽(Zhou L) 等. 中华器官移植杂志(Chinese Journal of Organ Transplantation) ,1995 , 16(4) : 159 —161
[70] 刘群(Liu Q) , 薛伟明(Xue W M) , 马小军(Ma X J) 等. 高等学校化学学报(Chemical Journal of Chinese Universities) ,2002 , 23(7) : 1417 —1420
[71] Liu X D , Xue W M, Ma X J , et al . Carbohydr. Polym. , 2004 ,56(4) : 459 —464
[72] Goosen M F A , King G A , Mcknight C A , et al . J . Membr.Sci . , 1989 , 41 : 323 —343
[73] Kang I K, Moon J S , Jeon H M, et al . J . Mater. Sci . Mater.Med. , 2005 , 16(6) : 533 —539
[74] Sakai S , Ono T , Ijima H , et al . Ann. N. Y. Acad. Sci . ,2001 , 944 : 277 —283
[75] Peirone M, Ross C J D , Chang P L , et al . J . Biomed. Mater.Res. , 1998 , 42(4) : 587 —596
[76] Goosen M F A. Ann. N. Y. Acad. Sci . , 1999 , 875 : 84 —104
[77] Kwok W Y, Kiparissides C , Goosen M F A , et al . Can. J .Chem. Eng. , 1991 , 69 : 361 —370
[78] 解玉冰(Xie YB) , 马小军(Ma X J ) , 王毓福(Wang Y F)等. 膜科学与技术(Membrane Science and Technology) , 1997 ,17(4) : 51 —56
[79] 何洋(He Y) , 解玉冰(Xie Y B) , 马小军(Ma X J ) 等. 高等学校化学学报(Chemical Journal of Chinese Universities) ,2000 , 21(2) : 278 —282
[80] Qi W T , Ma J , Ma X J , et al . J . Membr. Sci . , 2006 , 269 :126 —132
[81] Dove A. Nat . Biotechnol . , 2002 , 20 : 339 —343
[82] Chang T M S. Artif . Organs , 2004 , 28(3) : 265 —270
[83] Sun YL , Ma X J , Sun A M, et al . J . Clin. Invest . , 1996 , 98(6) : 1417 —1422
[84] Garfinkel M R , Harland R C , Opara E C. J . Surg. Res. , 1998 ,76 : 7 —10
[85] Lanza R P , Jackson R , Sullivan A , et al . Transplantation , 1999 ,67 (8) : 1105 —1111
[86] Hamid M, McCluskey J T , Flatt P R , et al . Cell Biol . Int . ,2001 , 25(6) : 553 —556
[87] De Vos P , van Hoogmoed C G, van Zanten J , et al . Biomaterials ,2003 , 24 : 305 —312
[88] Calafiore R , Basta G, Luca G, et al . Biotechnol . Appl .Biochem. , 2004 , 39 : 159 —164
[89] Schneider S , Feilen P J , Brunnenmeier F , et al . Diabetes , 2005 ,54 : 687 —693
[90] Soon-Shiong P , Heintz R E , Merideth N , et al . Lancet , 1994 ,343 : 950 —951
[91] Soon-Shiong P. Adv. Drug Delivery Rev. , 1999 , 35 : 259 —270
[92] Chen J P , Chu I M, Shiao M Y, et al . J . Ferment . Bioeng. ,1998 , 86 (2) : 185 —190
[93] Winn S R , Tresco P A , Zielinski B , et al . Exp. Neurol . , 1991 ,113(3) : 322 —329
[94] Lindner M D , Emerich D F. Cell Transplant . , 1998 , 7 ( 2) :165 —174
[95] Date I , Shingo T , Yoshida H , et al . Cell Transplant . , 2000 , 9(5) : 705 —709
[96] 薛毅珑(Xue Y L) , 王振福(Wang Z F) , 李新建(Li X J )等. 解放军医学杂志(Medical Journal of People's Liberation Army) , 1999 , 24(4) : 238 —241
[97] Xue Y L , Wang Z F , Zhong D G, et al . Artif . Cell Blood Substit . Immobil . Biotechnol . , 2000 , 28 (4) : 337 —345
[98] Hanahan D , Folkman J . Cell , 1996 , 86 : 353 —364
[99] O'Reilly M S , Holmgren L , Folkman J , et al . Cell , 1994 , 79 :315 —328
[100] O'Reilly M S , Boehm T , Folkman J , et al . Cell , 1997 , 88 :277 —285
[101] Joki T , Machluf M, Carroll R S , et al . Nat . Biotechnol . , 2001 ,19 : 35 —39
[102] Cirone P , Shen F , Chang P L. Cancer Gene Ther. , 2005 , 12(4) : 369 —380
[103] Dixit V , Darvasi R , Gitnick G, et al . Hepatology , 1990 , 12(6) : 1342 —1349
[104] Dixit V , Arthur M, Gitnick G. Biomater. Artif . Cells Immobil .Biotechnol . , 1993 , 21(2) : 119 —133
[105] Umehara Y, Hakamada K, Seino K, et al . Surgery , 2001 , 130(3) : 513 —520
[106] Prakash S , Chang T M S. Nat . Med. , 1996 , 2(8) : 883 —887
[107] Prakash S , Chang T M S. Artif . Cells Blood Substit . Immobil .Biotechnol . , 1998 , 26 (1) : 35 —51
[108] Prakash S , Chang T M S. Int . J . Artif . Organs , 2000 , 23 (7) :429 —435
[109] 于炜婷(Yu W T) , 雄鹰(Xiong Y) , 马小军(Ma X J ) 等.高等学校化学学报(Chemical Journal of Chinese Universities) ,2004 , 25(7) : 1381 —1383
[110] Zhang X L , Wang W, Ma X J , et al . Biotechnol . Prog. , 2005 ,21 : 1289 —1296
[111] Fuchs E , Tumbar T , Guasch G. Cell , 2004 , 116 : 769 —778
[112] Wang X L , Wang W, Ma X J , et al . Biotechnol . Prog. , 2006 ,22 : 791 —800
[113] Langer R , Tirrell D A. Nature , 2004 , 428 : 487 —492
[114] 刘袖洞(Liu X D) , 马小军(Ma X J) , 袁权(Yuan Q) . 化工学报(Journal of Chemical Industry and Engineering) , 2005 , 56 :955 —961
[115] Hari P R , Chandy T , Sharma C P. J . Appl . Polym. Sci . , 1996 ,59 : 1795 —1801
[116] Ramadas M, Paul W, Dileep K J , et al . J . Microencapsul . ,2000 , 17 : 405 —411
[117] Vandenberg G W, Drolet C , de la Noüe J , et al . J . Control .Release , 2001 , 77 : 297 —307
[118] Lin Y H , Liang H F , Sung H W, et al . Biomaterials , 2005 , 26 :2105 —2113
[119] Jani P , Halbert G W, Florence A T , et al . J . Pharm.Pharmacol . , 1990 , 42 : 821 —826
[120] Ritger P L , Peppas N A. J . Control . Release , 1987 , 5 : 23 —36
[121] Umamaheshwari R B , Jain S , Jain N K. Drug Delivery , 2003 ,10 : 151 —160
[122] Zheng J H , Liu C W, Ma X J , et al . J . Appl . Polym. Sci . ,2006 , 102 (3) : 2226 —2232
[123] 袁静( Yuan J ) . 中国野生植物资源( Chinese Wild Plant Resources) , 1997 , 16 : 8 —11
[124] 李胜(Li S) , 许有威(Xu Y W) , 马小军(Ma X J) 等. 中国医药工业杂志(Chinese Journal of Pharmaceuticals) , 2004 , 35 :657 —660
[125] Orive G, Hernández R M, Pedraz J L , et al . Nat . Med. , 2003 ,9 (1) : 104 —107
[126] Klêck G, Frank H , Zimmermann U , et al . Appl . Microbiol .Biotechnol . , 1994 , 40 : 638 —643
[127] Zimmermann H , Zimmermann D , Zimmermann U , et al . J .Mater. Sci . 2Mater. Med. , 2005 , 16 : 491 —501
[128] Orive G, Ponce S , Pedraz J L , et al . Biomaterials , 2002 , 23 :3825 —3831
[129] De Vos P , de Haan B J , van Schifgaarde R , et al . Diabetologia ,1997 , 40 : 262 —270
[130] De Vos P , de Haan B J , van Schifgaarde R. Biomaterials , 1997 ,18 : 273 —278
[131] Kulseng B , Skj?k-Br·k G, Ryan L , et al . Transplantation ,1999 , 67 : 978 —984
[132] Soon-Shiong P , Otterlie M, Skj?k-Br·k G, et al . Transplant .Proceedings , 1991 , 23(1) : 758 —759
[133] Venegas M, Matsuhiro B , Edding E. Botanica Marina , 1993 , 36 :47 —51
[134] King A , Strand B , Rokstad A M, et al . J . Biomed. Mater.Res. , 2003 , 64 : 533 —539
[135] De Vos P , de Haan B J , van Schilfgaarde R. Transplantation ,1996 , 62 : 893 —899
[136] Zimmermann U , Thürmer F , Jork A , et al . Ann. N. Y. Acad.Sci . , 2001 , 944 : 199 —215
[137] Dornish M, Kaplan D , Skaugrud O. Ann. N. Y. Acad. Sci . ,2001 , 944 : 388 —397
[1] 胡子涛, 丁寅. 基于共价有机框架材料的纳米体系在生物医学中的应用[J]. 化学进展, 2021, 33(11): 1935-1946.
[2] 闻静, 李禹红, 王莉, 陈秀楠, 曹旗, 何乃普. 基于壳聚糖二氧化碳智能材料[J]. 化学进展, 2020, 32(4): 417-422.
[3] 张赛晖, 王悦, 柳开鹏, 王捷. 聚电解质型正渗透汲取液[J]. 化学进展, 2019, 31(7): 969-979.
[4] 姚东梅, 张玮琦, 徐谦, 徐丽, 李华明, 苏华能. 磷酸掺杂聚苯并咪唑高温膜燃料电池膜电极[J]. 化学进展, 2019, 31(2/3): 455-463.
[5] 徐子悦, 张运昌, 林佳乐, 王辉, 张丹维, 黎占亭. 药物输送体系构筑中的超分子组装策略[J]. 化学进展, 2019, 31(11): 1540-1549.
[6] 张瑞, 刘璇, 纪红兵*. 天然香料纳微胶囊中间体[J]. 化学进展, 2018, 30(1): 29-43.
[7] 王欢, 商珞然, 顾笑晓, 戎非, 赵远锦. 编码微载体的制备及其生物医学应用[J]. 化学进展, 2017, 29(10): 1159-1172.
[8] 宋萍, 叶德楷, 宋世平, 王丽华, 左小磊. DNA水凝胶的制备及生物应用[J]. 化学进展, 2016, 28(5): 628-636.
[9] 高鹏, 高彬彬, 高建强, 张锴, 杨勇平, 陈鸿伟. 壳聚糖及其复合物对水中汞离子的脱除[J]. 化学进展, 2016, 28(12): 1834-1846.
[10] 慈吉良, 康宏亮, 刘晨光, 贺爱华, 刘瑞刚. 两性离子聚合物的抗蛋白质吸附机理及其应用[J]. 化学进展, 2015, 27(9): 1198-1212.
[11] 熊丽娜, 张雪勤, 孙莹, 杨洪. 全共轭嵌段共聚物的合成组装与应用[J]. 化学进展, 2015, 27(12): 1774-1783.
[12] 王奕寒, 脇坂港. 纳米纤维制备工艺进展及其对壳聚糖的适用性分析[J]. 化学进展, 2014, 26(11): 1821-1831.
[13] 黎燕, 黄卫, 黄平, 朱新远, 颜德岳. 抗肿瘤药物输送系统[J]. 化学进展, 2014, 26(08): 1395-1408.
[14] 张磊, 刘晓燕, 沈晶晶, 卢晓梅, 范曲立, 黄维. 纳米颗粒在抗癌药物可控靶向释放中的应用[J]. 化学进展, 2013, 25(08): 1375-1382.
[15] 刘欣, 赵海雷, 解晶莹, 汤卫平, 潘延林, 吕鹏鹏. 锂离子电池高比容量负极用粘结剂[J]. 化学进展, 2013, 25(08): 1401-1410.