Poly(ethylene glycol)-based polymer carrier of doxorubicin degradable by both enzymatic and chemical hydrolyses

被引:10
作者
Pechar, M [1 ]
Braunová, A [1 ]
Ulbrich, K [1 ]
机构
[1] Acad Sci Czech Republ, Inst Macromol Chem, CR-16206 Prague, Czech Republic
关键词
drug delivery systems; cancer therapy; doxorubicin; poly(ethylene glycol); peptide synthesis; polymer-supported drugs; antineoplastics; cytostatics; biodegradable polymers;
D O I
10.1135/cccc20050327
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The synthesis and characterization of a water-soluble biodegradable multiblock polyurethane based on poly(ethylene glycol) blocks interconnected by a pentapeptide derivative N, N'-bis(aspartylprolyl)lysine is described. The pentapeptide linkages are susceptible both to chemical hydrolysis in neutral and mild acid medium (pH 5) and to enzymatic degradation by lysosomal enzyme cathepsin B. Anti-cancer drug doxorubicin was attached to a hydrazide derivative of the polymer via a hydrolytically labile hydrazone bond. Both the pH-triggered hydrolytic release of the drug and the degradation of the polymer carrier by enzymatic and chemical hydrolysis were studied using liquid chromatography.
引用
收藏
页码:327 / 338
页数:12
相关论文
共 24 条
  • [1] Decreased binding to proteins and cells of polymeric gene delivery vectors surface modified with a multivalent hydrophilic polymer and retargeting through attachment of transferrin
    Dash, PR
    Read, ML
    Fisher, KD
    Howard, KA
    Wolfert, M
    Oupicky, D
    Subr, V
    Strohalm, J
    Ulbrich, K
    Seymour, LW
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (06) : 3793 - 3802
  • [2] A novel acidotropic pH indicator and its potential application in labeling acidic organelles of live cells
    Diwu, ZJ
    Chen, CS
    Zhang, CL
    Klaubert, DH
    Haugland, RP
    [J]. CHEMISTRY & BIOLOGY, 1999, 6 (07): : 411 - 418
  • [3] New HPMA copolymers containing doxorubicin bound via pH-sensitive linkage:: synthesis and preliminary in vitro and in vivo biological properties
    Etrych, T
    Jelínková, M
    Ríhová, B
    Ulbrich, K
    [J]. JOURNAL OF CONTROLLED RELEASE, 2001, 73 (01) : 89 - 102
  • [4] ETTINGER LJ, 1995, CANCER, V75, P1176, DOI 10.1002/1097-0142(19950301)75:5<1176::AID-CNCR2820750519>3.0.CO
  • [5] 2-Y
  • [6] A versatile system for receptor-mediated gene delivery permits increased entry of DNA into target cells, enhanced delivery to the nucleus and elevated rates of transgene expression
    Fisher, KD
    Ulbrich, K
    Subr, V
    Ward, CM
    Mautner, V
    Blakey, D
    Seymour, LW
    [J]. GENE THERAPY, 2000, 7 (15) : 1337 - 1343
  • [7] Pegylated liposomal doxorubicin: Metamorphosis of an old drug into a new form of chemotherapy
    Gabizon, AA
    [J]. CANCER INVESTIGATION, 2001, 19 (04) : 424 - 436
  • [8] Doxorubicin-loaded poly(ethylene glycol)-poly(β-benzyl-l-aspartate) copolymer micelles:: their pharmaceutical characteristics and biological significance
    Kataoka, K
    Matsumoto, T
    Yokoyama, M
    Okano, T
    Sakurai, Y
    Fukushima, S
    Okamoto, K
    Kwon, GS
    [J]. JOURNAL OF CONTROLLED RELEASE, 2000, 64 (1-3) : 143 - 153
  • [9] MAEDA H, 1989, CRIT REV THER DRUG, V6, P193
  • [10] Structure-activity relationships of poly(L-lysines):: effects of pegylation and molecular shape on physicochemical and biological properties in gene delivery
    Männistö, M
    Vanderkerken, S
    Toncheva, V
    Elomaa, M
    Ruponen, M
    Schacht, E
    Urtti, A
    [J]. JOURNAL OF CONTROLLED RELEASE, 2002, 83 (01) : 169 - 182