Interaction of a lipid-membrane destabilizing enzyme with PEG-liposomes

被引:15
作者
Jorgensen, K
Kiebler, T
Hylander, I
Vermehren, C
机构
[1] Royal Danish Sch Pharm, Dept Pharmaceut, DK-2100 Copenhagen, Denmark
[2] Tech Univ Denmark, Dept Chem, DK-2800 Lyngby, Denmark
关键词
PEG-liposome; drug-delivery; phospholipase A(2); liposome-degradation; enzyme-membrane interaction;
D O I
10.1016/S0378-5173(99)00036-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Polymer grafted PEG-liposomes have come into use as drug-delivery systems with improved therapeutic profiles. However, very little is known about the morphological instability of PEG-liposomes due to enzymatic degradation. To gain further insight into the effect of PEG lipopolymer-concentration on the catalytic activity of a liposome-degrading enzyme, phospholipase A(2) (PLA(2))-catalyzed phospholipid hydrolysis of PEG-liposomes has been investigated. The temperature dependence of the PLA(2) lag-time, denoting the rime required before a sudden increase in enzymatic activity takes place, has been determined for submicellar amounts of dipalmitoylphosphatidylethanolaminyl-poly-(ethylene glycol) (DPPE-PEG(2000)) incorporated into unilamellar dipalmitoylphosphatidylcholine (DPPC)-liposomes. The measurements demonstrate a significant reduction in the lag-time over broad temperature ranges. The results suggest that a close relationship exists between PLA(2) catalyzed lipid hydrolysis and lipid-membrane composition, which moreover is of major importance for the overall morphological stability and the release of encapsulated material from the polymer-grafted PEG-liposomes. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:21 / 24
页数:4
相关论文
共 17 条
[1]   The effects of ethylene oxide containing lipopolymers and tri-block copolymers on lipid bilayers of dipalmitoylphosphatidylcholine [J].
Baekmark, TR ;
Pedersen, S ;
Jorgensen, K ;
Mouritsen, OG .
BIOPHYSICAL JOURNAL, 1997, 73 (03) :1479-1491
[2]   MOLECULAR MECHANISM OF THE LIPID VESICLE LONGEVITY INVIVO [J].
BLUME, G ;
CEVC, G .
BIOCHIMICA ET BIOPHYSICA ACTA, 1993, 1146 (02) :157-168
[3]   The effect of increasing membrane curvature on the phase transition and mixing behavior of a dimyristoyl-sn-glycero-3-phosphatidylcholine/distearoyl-sn-glycero-3-phosphatidylcholine lipid mixture as studied by Fourier transform infrared spectroscopy and differential scanning calorimetry [J].
Brumm, T ;
Jorgensen, K ;
Mouritsen, OG ;
Bayerl, TM .
BIOPHYSICAL JOURNAL, 1996, 70 (03) :1373-1379
[4]  
BURRACK WR, 1993, BIOCHEMISTRY-US, V32, P583
[5]  
CHONN A, 1992, J BIOL CHEM, V267, P18759
[6]  
DENKAMP JAF, 1974, BIOCHIM BIOPHYS ACTA, V345, P253
[7]  
HANSEN HS, 1995, TEMANORD, V624, P221
[8]  
Honger T, 1997, METHOD ENZYMOL, V286, P168
[9]   Systematic relationship between phospholipase A(2) activity and dynamic lipid bilayer microheterogeneity [J].
Honger, T ;
Jorgensen, K ;
Biltonen, RL ;
Mouritsen, OG .
BIOCHEMISTRY, 1996, 35 (28) :9003-9006
[10]   EFFECT OF BILAYER COMPOSITION ON THE PHASE-BEHAVIOR OF LIPOSOMAL SUSPENSIONS CONTAINING POLY(ETHYLENE GLYCOL)-LIPIDS [J].
HRISTOVA, K ;
KENWORTHY, A ;
MCINTOSH, TJ .
MACROMOLECULES, 1995, 28 (23) :7693-7699