Using polyethylene glycol (PEG) to functionalize liposomes improves their stealth properties and stability in blood. However, PEG is known to induce the accelerated blood clearance (ABC) phenomenon, which occurs for multiple doses owing to anti-PEG IgM being produced after the initial injection. In this study, as an alternative to PEG, polysarcosine (PSar) was selected owing to its low antigenicity and its highly dense chains with controllable lengths, similar to PEG. Furthermore, we directly evaluate the potential of PSar for avoiding the ABC phenomenon by comparing PSar with PEG on the same liposome platform, which has similar physicochemical properties such as hydrophobic region, membrane fluidity, and size. PEG- and PSar-liposomes were prepared and characterized for comparison. PSar-liposomes showed similar physicochemical properties to PEG-liposomes in terms of size control, zeta potential, membrane polarity, and fluidity; however, ELISA results showed noticeably lower levels and faster production speeds of both IgM and IgG for PSar-liposomes than for PEG-liposomes. In addition, a pharmacokinetics experiment with multiple injections showed that PSar-PE coating of liposomes may help to circumvent the ABC phenomenon.

中文翻译：

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通过脂质体的聚肌氨酸涂层避免加速的血液清除现象。

使用聚乙二醇（PEG）对脂质体进行功能化可改善其隐身性和血液稳定性。但是，已知PEG会引起加速的血液清除（ABC）现象，由于在首次注射后会产生抗PEG IgM，因此在多剂量情况下都会发生。在这项研究中，与PEG相似，由于聚肌氨酸（PSar）的低抗原性和长度可控制的高密度链而选择了聚肌氨酸（PSar）。此外，我们通过在相同脂质体平台上比较PSar和PEG，直接评估PSar避免ABC现象的潜力，该平台具有相似的理化特性，例如疏水区域，膜流动性和大小。制备PEG-和PSar-脂质体并进行表征以进行比较。PSar脂质体在大小控制，ζ电位，膜极性和流动性方面表现出与PEG脂质体相似的理化性质。但是，ELISA结果显示PSar脂质体的IgM和IgG的水平明显低于PEG脂质体，并且生产速度更快。此外，多次注射的药代动力学实验表明，脂质体的PSar-PE涂层可能有助于规避ABC现象。