Association of hydrophobically-modified poly(ethylene glycol) with fusogenic liposomes

被引:47
作者
Auguste, DT
Prud'homme, RK [1 ]
Ahl, PL
Meers, P
Kohn, J
机构
[1] Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA
[2] Elan Pharmaceut, Drug Delivery, Princeton, NJ 08540 USA
[3] Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2003年 / 1616卷 / 02期
关键词
fusogenic liposome; hydrophobically modified PEG; liposome protection; complement assay; comb-graft; protein shielding;
D O I
10.1016/j.bbamem.2003.08.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We present results on using cooperative interactions to shield liposomes by incorporating multiple hydrophobic anchoring sites on polyethylene glycol (PEG) polymers. The hydrophobically-modified PEGs (HMPEGs) are comb-graft polymers with strictly alternating monodisperse PEG blocks (M-w=6, 12, or 35 kDa) bonded to C18 stearylamide hydrophobes. Cooperativity is varied by changing the degree of oligomerization at a constant ratio of PEG to stearylamide. Fusogenic liposomes prepared from N-C12-DOPE:DOPC 7:3 (mol:mol) were equilibrated with HMPEGs. Affinity for polymer association to liposomes increases with the degree of oligomerization; equilibrium constants (given as surface coverage per equilibrium concentration of free polymer) for 6 kDa PEG increased from 6.1+/-0.8 (mg/m(2))/(mg/ml) for 2.5 loops to 78.1 +/- 12.2 (mg/m(2))/(mg/ml) for 13 loops. In contrast, the equilibrium constant for distearoylphosphatidylethanolaminepoly(ethylene glycol) (DSPE-PEG5k) was 0.4 +/- 0.1 (mg/m(2))/(mg/ml). The multi-loop HMPEGs demonstrate higher levels of protection from complement binding than DSPE-PEG5k. Greater protection does not correlate with binding strength alone. The best shielding was by HMPEG6k-DP3 (with three 6 kDa PEG loops), suggesting that PEG chains with adequate surface mobility provide optimal protection from complement opsonization. Complement binding at 30 min and 12 h demonstrates that protection by multi-looped PEGs is constant whereas DSPE-PEG5k initially protects but presumably partitions off of the surface at longer times. (C) 2003 Published by Elsevier B.V.
引用
收藏
页码:184 / 195
页数:12
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