Optimization of lipodisk properties by modification of the extent and density of the PEG corona

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• 作者：Malin Morin Zetterberg^a ; ^{malin.zetterberg@kemi.uu.se" class="auth_mail" title="E-mail the corresponding author} ; Sara Ahlgren^a ; ^{sara.ahlgren@kemi.uu.se" class="auth_mail" title="E-mail the corresponding author} ; Ví ; ctor Agmo Herná ; ndez^a ; ^{victor.agmo@kemi.uu.se" class="auth_mail" title="E-mail the corresponding author} ; Nagma Parveen^b ; ^{nagma.parveen@chalmers.se" class="auth_mail" title="E-mail the corresponding author} ; Katarina Edwards^a ; ^{katarina.edwards@kemi.uu.se" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Lipid self-assembly ; Bilayer disks ; Biomimetic membranes ; Surface immobilization ; Drug delivery ; Nanocarriers ; Specific targeting
• 刊名：Journal of Colloid and Interface Science
• 出版年：2016
• 出版时间：15 December 2016
• 年：2016
• 卷：484
• 期：Complete
• 页码：86-96
• 全文大小：2479 K

文摘

Lipodisks are nanosized flat, circular, phospholipid bilayers that are edge-stabilized by polyethylene glycol-conjugated lipids (PEG-lipids). Over the last decade, lipodisks stabilized with PEG of molecular weight 2000 or 5000 have been shown to hold high potential as both biomimetic membranes and drug carriers. In this study we investigate the possibilities to optimize the properties of the lipodisks, and widen their applicability, by reducing the PEG molecular weight and/or the density of the PEG corona.

Results obtained by cryo-transmission electron microscopy and dynamic light scattering show that stable, well-defined lipodisks can be produced from mixtures of distearoylphosphatidylcholine (DSPC) and distearoylphosphatidylethanolamine conjugated to PEG of molecular weight 1000 (DSPE-PEG₁₀₀₀). Preparations based on the use of DSPE-PEG₇₅₀ tend, in contrast, to be polydisperse in size and structure. By comparing immobilization of lipodisks stabilized with DSPE-PEG₁₀₀₀, DSPE-PEG_2000, and DSPE-PEG₅₀₀₀ to porous and smooth silica surfaces, we show that the amount of surface bound disks can be considerably improved by the use of PEG-lipids with reduced molecular weight. Further, a modified preparation protocol that enables production of lipodisks with very low PEG-lipid content is described. The reduced PEG density, which facilitates the incorporation of externally added ligand-linked PEG-lipids, is shown to be beneficial for the production of targeting lipodisks.