Association of hydrophobically-modified poly(ethylene glycol) with fusogenic liposomes
Association of hydrophobically-modified poly(ethylene glycol) with fusogenic liposomes
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DOI：
10.1016/j.bbamem.2003.08.007
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发表时间：
2003-10-13
影响因子：
3.4
通讯作者：
Kohn, J
中科院分区：
文献类型：
--
作者：
Auguste, DT;Prud'homme, RK;Kohn, J
我们目前的结果使用合作的相互作用，屏蔽脂质体，将多个疏水锚定位点聚乙二醇（PEG）聚合物。疏水改性的PEG（HMPEG）是具有严格交替的单分散PEG嵌段（M-w=6、12或35 kDa）的梳形接枝聚合物，其键合到C18硬脂酰胺疏水物。通过在PEG与硬脂酰胺的恒定比率下改变低聚程度来改变协同性。用HMPEG平衡由N-C12-DOPE：DOPC 7：3（mol：mol）制备的融合脂质体。聚合物与脂质体结合的亲和力随着寡聚化程度的增加而增加; 6 kDa PEG的平衡常数（以每平衡浓度的游离聚合物的表面覆盖率给出）从2.5个环的6.1+/-0.8（mg/m（2））/（mg/ml）增加到13个环的78.1 +/-12.2（mg/m（2））/（mg/ml）。相比之下，二硬脂酰磷脂酰乙醇胺聚（乙二醇）（DSPE-PEG 5 k）的平衡常数为0.4 ± 0.1（mg/m2）/（mg/ml）。更好的保护并不仅仅与结合强度相关。最好的屏蔽是通过HMPEG 6 k-DP 3（具有三个6 kDa PEG环），这表明具有足够表面流动性的PEG链提供了最佳的保护免受补体调理作用。在30分钟和12小时的补体结合表明，通过多环PEG的保护是恒定的，而DSPE-PEG 5 k最初保护，但可能在更长的时间内从表面分离。(C)2003年由Elsevier B. V.出版
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.