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化学进展 2011, Vol. 23 Issue (8): 1747-1754 前一篇   后一篇

• 综述与评论 •

白蛋白作为药物载体的研究

张建军1, 高缘2*, 孙婉瑾2*   

  1. 1. 中国药科大学药学院 南京 210009;
    2. 中国药科大学中药学院 南京 210009
  • 收稿日期:2010-11-01 修回日期:2011-03-01 出版日期:2011-08-24 发布日期:2011-07-25
  • 通讯作者: 高缘, 孙婉瑾 E-mail:amicute@163.com; sunwanjin@126.com
  • 基金资助:

    国家"重大新药创制"科技重大专项新制剂与新释药系统技术平台(No. 2009ZX09310-004) 和江苏省自然科学基金项目(No. SBK20080571) 资助

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Albumin as Drug Carriers

Zhang Jianjun1, Gao Yuan2*, Sun Wanjin2*   

  1. 1. School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China;
    2. School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China
  • Received:2010-11-01 Revised:2011-03-01 Online:2011-08-24 Published:2011-07-25

白蛋白作为药物载体的应用已越来越广泛,其载药方式主要有两种:一是使药物和白蛋白载体间产生分子链接形成白蛋白化药物,即化学偶联的白蛋白载药;二是依赖蛋白与药物的相互作用将药物包埋于白蛋白纳米颗粒中,即物理结合的白蛋白载药。化学偶联白蛋白可改善药物的药代动力学特性,其中又可分为外源性白蛋白与药物耦合、前体药物进入体内与内源性白蛋白结合、蛋白及多肽类药物的白蛋白化。物理结合则可优化药物某些体外特性,如提高溶解性、稳定性等。基于临床应用的需求,作为载体的白蛋白正历经着修饰及改性的研究热潮。本文总结了近年来白蛋白载药技术的发展及白蛋白的修饰改性现状。

关键词： 白蛋白, 载体, 化学偶联, 前体药物, 修饰改性

Albumin is the chief circulating protein which plays more and more important roles as drug carriers in pharmaceutical uses nowadays. Two basic drug delivery technologies can be distinguished: albumin chemically coupling with drugs to form albumin-drug conjugates; encapsulation of drugs into albumin nanoparticles by physical interaction. Exogenous albumin chemically coupling with drugs, endogenous albumin binding prodrugs and therapeutic peptides or proteins binding to albumin are the three forms of albumin-drug conjugates which possess the ability of improving the pharmacokinetic properties of drugs. Physical integration with albumin is another albumin based drug delivery technology that can promote some characteristics of the drugs in vitro like enhancing their solubility and stability. This review gives an account of different drug delivery systems which make use of albumin as drug carriers with a focus on such systems that successfully solved the issues and have reached an advanced stage in their R & D processes. The application of albumin as drug carriers still has some defects including low drug load and week targeting features. Constantly a large number of modifications and reshaping of albumin are carried out in order to solve the problems, some of which are also involved in this review because the requirements of clinical developments.

Contents
1 Introduction
2 Biology basis for albumin as drug carriers
3 Chemical conjugates with albumin as drug carriers
3.1 Exogenous albumin-drug conjugates
3.2 Endogenous albumin binding prodrugs
3.3 Albumin binding therapeutic peptides or proteins
4 Physical compounds with albumin as drug carriers
4.1 Albumin nanoparticles
4.2 Albumin microspheres
5 Modifications and reshaping of albumin
6 Summary and outlook

Key words: albumin, drug carriers, chemical conjugates, prodrugs, modification

中图分类号: 

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[1] Thakkar H, Sharma R K, Mishra A K, Chuttani K, Murthy R R. AAPS. Pharmscitech., 2005, 6(1): E65-E73
[2] Muller B G. Pharm. Res., 1996, 13(1): 32-37
[3] Maia C S. J. drug Target., 2002, 10(6): 489-495
[4] Xiao J B, Chen J W. J. Photoch. Photobio. A, 2007, 191(2/3): 222-227
[5] Zhao H W, Ge M. Spectrochim. Acta A, 2006, 65(3/4): 811-817
[6] Sun S F, Zhou B, Hou H N, Liu Y, Xiang G Y. Int. J. Biol. Macromol., 2006, 9(4/5): 197-200
[7] Ulrich K H, Victor T G C. Masakio. Biol. Pharm. Bull., 2002, 25 (6): 695-704
[8] Vermeulenj N, Meljer D K, Over J, Lange J, Proost J H, Bakker H I, Beljaars L, Wit F W, Prins J M. Antivir. Ther., 2007, 12 (2): 273-278
[9] Allen T M, Cullis P R. Science, 2004, 303(5665): 1818-1822
[10] Kratz F. J. Control. Release, 2008, 132(3): 171-183
[11] Ohhashi T, Mizuno R, Ikomi F, Kawai Y. Pharmacol. Ther., 2005, 105 (2): 165-188
[12] Kratz F, Beyer U. Drug Deliv., 1998, 5(4): 281-299
[13] Matthew R D, Wenge L, Charles R M, Dewhirst M W, Yuan F, Chilkoti A. J. Natl. Cancer Inst., 2006, 98(5): 335-344
[14] Stehle G, Sinn H, Wunder A, Schrenk H H, Stewart J C M, Hartung G, Maier-Borst W, Heene D L. Crit. Rev. Oncol., 1997, 26(2): 77-100
[15] Wunder A, Stehle G, Schrenk H H, Hartung G, Heene D L, Maier-Borst W, Sinn H. Int. J. Cancer, 1998, 76(6): 884-890
[16] Greenfield R S, Kaneko T, Daues A, Edson M A, Fitzgerald K A, Olech L J, Grattan J A, Spitalny G L, Braslawsky G R. Cancer Res., 1990, 50: 6600-6607
[17] Di Stefano G, Kratz F, Lanza M, Fiume L. Dig. Liver Dis., 2003, 35(6): 428-433
[18] Gene M, Michael A. Pharmacol. Therapeut., 1999, 83(2): 67-123
[19] Burger A M, Hartung G, Stehle G, Sinn H, Fiebig H H. Int. J. Cancer, 2001, 92(5): 718-724
[20] Bolling C, Graefe T, Lübbing C, Jankevicius F, Uktveris S, Cesas A, Meyer-Moldenhauer W H, Starkmann H, Weigel M, Burk K, Hanauske A R. Invest New Drugs, 2006, 24(6): 521-527
[21] 詹新立(Zhan X L ), 周江南(Zhou J N), 赵自平(Zhao Z P), 蒋欣(Jiang X), 李官成(Li G C). 中华实验外科杂志(Chinese Journal of Experimental Surgery), 2004, 21(3): 345-347
[22] 李安民(Li A M), 张传秀(Zhang C X), 富向平(Fu X P), 张志文(Zhang Z W), 薛菁晖(Xue Q H), 闫润民 (Yan R M), 易林华(Yi L H). 中国微创外科杂志(Chinese Journal of Minimally Invasive Surgery), 2005, 5(5): 409-411
[23] 于耀宇(Yu Y Y), 李安民(Li A M), 张翔(Zhang X), 易声禹(Yi S Y), 张剑宁 (Zhang J N), 步星耀(Bu X Y), 陈义军(Chen Y J), 易林华(Yi L H). 中华实验外科杂志(Chinese Journal of Experimental Surgery), 2000, 17(3): 257-258
[24] Wunder A, Müller-Ladner U, Stelzer E H, Funk J, Neumann E, Stehle G, Pap T, Sinn H, Gay S, Fiehn C. J. Immunol., 2003, 170(9): 4793-4801
[25] Fiehn C, Müller-Ladner U, Gay S, Krienke S, Freudenberg-Konrad S, Funk J, Ho A D, Sinn H, Wunder A. Rheumatology, 2004, 43(9): 1097-1105
[26] Lermo A, Fabiano S, Hernández S, Galve R, Marco M P, Alegret S, Pividori M I. Biosens. Bioelectron., 2009, 24(7): 2057-2063
[27] Kitagawa T, Kanamaruk T, Wakamatsus H, Kato H, Yano S, Asanuma Y. J. Biochem., 1978, 84(2): 491-494
[28] Fiehn C, Neumann E, Wunder A, Krienke1 S, Gay S, Müller-Ladner U. Ann. Rheum. Dis., 2004, 63(7): 884-886
[29] Kratz F, Mueller-Driver R, Hofmann I, Drevs J, Unger C. J. Med. Chem., 2000, 43(7): 1253-1256
[30] Kratz F, Warnecke A, Scheuermann K, Stockmar C, Schwab J, Lazar P, Drückes P, Esser N, Drevs J, Rognan D, Bissantz C, Hinderling C, Folkers G, Fichtner I, Unger C. J. Med. Chem., 2002, 45(25): 5523-5533
[31] Carla B, Luigi F, Michele B, Bertucci C, Farina C, Kratz F, Manerba M, Naldi M, Di Stefano G. Eur. J. Pharm. Sci., 2009, 38(3): 262-269
[32] Fiume L, Baglioni M, Bolondi L, Farina C, Di Stefano G. Drug Discov. Today, 2008, 13 (21/22): 1002-1009
[33] Kratz F. Expert Opin. Inv. Drug, 2007, 16(6): 855-866
[34] Kratz F, Mansour A, Soltau J, Warnecke A, Fichtner I, Unger C, Drevs J. Arch. Pharm., 2005, 338(10): 462-472
[35] Warnecke A, Fichtner I, Sass G, Kratz F. Arch. Pharm., 2007, 340(8): 389-395
[36] Subramanian G M, Fiscella M, Lamousé-Smith A, Zeuzem S, McHutchison J G. Nat. Biotechnol., 2007, 25(12): 1411-1419
[37] Christensen M, Knop F K. Current Diabetes Reports, 2010, 10(2): 124-132
[38] Nguyen A, Reyes A E, Zhang M, McDonald P, Wong W L, Damico L A, Dennis M S. Protein Eng. Des. Sel., 2006, 19(7): 291-297
[39] Swinnen S G, Snoek F J, Dain M P, DeVries J H, Hoekstra J B, Holleman F. Diabetes Technol. Therap., 2009, 11(11): 739-743
[40] Moghimi S M, Hunter A C, Murry J C. Pharmacol. Rev., 2001, 53(2): 283-318
[41] Teng K Y, Ze L, Guillaume W M, Au J L. Pharm. Res., 2005, 22(6): 867-874
[42] Ibrahim N K, Desai N, Legha S, Soon-Shiong P, Theriault R L, Rivera E, Esmaeli B, Ring S E, Bedikian A, Hortobagyi G N, Ellerhorst J A. Clin. Cancer Res., 2002, 8(5): 1038-1044
[43] Falciani M. US 2001046961, 2001
[44] Micha J P, Goldstein B H, Birk C L, Rettenmaier M A, Brown J V. Gynecol Oncol., 2006, 100(10): 437-438
[45] 舒文娟(Shu W J), 孙婉瑾(Sun W J), 樊伟明(Fan W M ), 张建军(Zhang J J), 高缘(Gao Y). 中国药科大学学报(Journal of China Pharmaceutical University), 2010, 41(3): 253-258
[46] Karmali P P, Kotamraju V R, Kastantin M, Black M, Missirlis D, Tirrell M, Ruoslahti E. Nanomedicine, 2009, 5(1): 73-82
[47] Lyster D M, Scott J R, Mincey E K, Morrison R T. Nucl. Med., 1974, 15(3): 198-199
[48] McDonagh J, Bolster A A, Murray T, Milligan M, Hilditch T E. Nucl. Med., 2004, 25(4): 423-424
[49] Dhabuwala A, Lamertom P, Stubbs R S. BMC Nucl. Med., 2005, 5: art. no. 7
[50] Korpanty G, Grayburn P A, Shohet R V, Brekken R A. Ultrasound Med. Biol., 2005, 31 (9): 1279-1283
[51] Aime S, Botta M, Crich S G, Giovenzana G B, Pagliarin R, Piccinini M, Sisti M, Terreno E. J. Biol. Inorg. chem., 1997, 2(4): 470-474
[52] Fiume L, Di Stefano G . Eur. J. Pharm. Sci., 2010, 40(4): 253-262
[53] Hu M, Scollard D, Chan C, Chen P, Vallis K, Reilly R M. Nucl. Med. Biol., 2007, 34 (8): 887-896
[54] Lin W, Garnett M C, Schacht E, Davisa S S, Illum L. Int. J. Pharm., 1999, 89 (2): 161-170
[55] Langer K, Coester C, Weber C, Kreuter J. Eur. J. Pharm. Biopharm., 2000, 49 (3): 303-307
[56] Ahmed N, Dobler D, Dean M, Thornalley P J. J. Biol. Chem., 2005, 280(7): 5724-5732
[57] Zhang L K, Hou S X, Mao S J, Wei D, Song X, Lu Y. Int. J. Pharm., 2004, 287(1/2): 155-162
[58] Han J H, Oh Y K, Kim D S, Kim C K. Int. J. Pharm., 1999, 188 (1): 39-47
[59] Fabrizio M, Franois L. Drug Discov. Today, 2004, 9(5): 219-228
[60] Makriyannis A, Guo J, Tian X. Life Sci., 2005, 77(14): 1605-1611
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摘要

白蛋白作为药物载体的研究