Institute of Organic Chemistry, Johannes Gutenberg-Universitat, Duesbergweg 10-14, Mainz, Germany.
Biomacromolecules. 2010 Mar 8;11(3):568-74. doi: 10.1021/bm901123j.
We describe the synthesis of linear-hyperbranched lipids for liposome preparation based on linear poly(ethylene glycol) (PEG) and hyperbranched polyglycerol (PG). Molecular weights were adjusted to values around 3000 g/mol with varying degrees of polymerization of the linear and the branched segments in analogy to PEG-based stealth lipids; polydispersities were generally low and below 1.3. The hydrophobic anchors were introduced into the lipid structures as initiators for the anionic polymerization of ethylene oxide and are either based on cholesterol or on different aliphatic glyceryl ethers. Complete incorporation of the apolar initiators was evidenced by MALDI-ToF analysis at all stages of the reaction. The linear-hyperbranched polyether lipid is incorporated as the polyfunctional shell in liposome formulations together with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The resulting liposomes were subsequently characterized via dynamic light scattering (DLS) and small angle neutron scattering (SANS) as well as transmission electron microscopy (TEM), demonstrating the formation of unilamellar liposomes in the size range of 40 to 50 nm.
我们描述了基于线性聚乙二醇(PEG)和超支化聚甘油(PG)的脂质体制备用线性-超支化脂质的合成。分子量通过线性和支化段的聚合度来调整,使其接近 3000g/mol,类似于基于 PEG 的隐形脂质;多分散性通常较低,低于 1.3。疏水性锚定基团被引入脂质结构中,作为环氧乙烷阴离子聚合的引发剂,它们要么基于胆固醇,要么基于不同的脂肪族甘油醚。通过 MALDI-ToF 分析在反应的所有阶段都证明了非极性引发剂的完全掺入。线性-超支化聚醚脂质与 1,2-二油酰基-sn-甘油-3-磷酸胆碱(DOPC)一起作为多功能壳层被包含在脂质体配方中。所得的脂质体随后通过动态光散射(DLS)和小角中子散射(SANS)以及透射电子显微镜(TEM)进行表征,证明了在 40 至 50nm 范围内形成了单层脂质体。
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