权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Search for strategy for abrogating the ABC phenomenon induced by repeated injections of PEGylated nanocarriers

寻找消除重复注射聚乙二醇化纳米载体引起的ABC现象的策略

基本信息

批准号：
23790047
负责人：
ICHIHARA Masako
金额：
$ 2.75万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2011
资助国家：
日本
起止时间：
2011 至 2012
项目状态：
已结题

项目摘要

PEG is considered as a bio-inert material, and surface modification with PEG can improve the immunogenicity and pharmacokinetics of the nanocarriers after intravenous injection. However, it has been reported that an intravenous injection of PEGylated liposomes triggers rapid clearance of a subsequent dose of the same liposomes with a certain interval (accelerated blood clearance (ABC) phenomenon). We recently showed that anti-PEG IgM induced by the first dose of PEGylated liposomes is responsible for the rapid clearance of the second dose. To date, there is no efficient approach to avoid the induction of anti-PEG IgM by injection of various PEGylated nanocarriers. In this study, we showed that surface-modification of PEGylated liposomes with Ganglioside, one of sialic acid derivatives, efficiently suppressed the induction of anti-PEG IgM after the injection of PEGylated liposomes via direct interaction with splenic B cells. Furthermore, we demonstrated that Ganglioside-modified PEGylated liposome present long circulating properties as PEGylated liposomes. These results suggest that surface-modification of the PEGylated liposomes with Ganglioside represents a promising strategy for abrogating the ABC phenomenon induced by repeated injections of PEGylated liposomes. The ABC phenomenon is a crucial issue in the development of novel colloidal nanocarriers, because their pharmacokinetics after injection must be reproducible in clinical settings to prevent unanticipated side effects and preserve pharmacological activity. Therefore, a strategy to avoid the induction of anti-PEG IgM by injection of PEGylated nanocarriers without significant compromising their in vivo behavior would be desirable for the further development of PEGylated nanocarriers in the future.

PEG被认为是一种生物惰性材料，用PEG进行表面修饰可以改善纳米载体的免疫原性和静脉注射后的药代动力学。然而，据报道，静脉内注射PEG化脂质体以一定的间隔触发后续剂量的相同脂质体的快速清除（加速血液清除（ABC）现象）。我们最近发现，第一剂PEG化脂质体诱导的抗PEG IgM负责第二剂的快速清除。迄今为止，还没有有效的方法来避免通过注射各种聚乙二醇化纳米载体诱导抗PEG IgM。在这项研究中，我们表明，表面修饰的PEG化脂质体与神经节苷脂，唾液酸衍生物之一，有效地抑制诱导抗PEG IgM后，注射PEG化脂质体通过直接与脾B细胞的相互作用。此外，我们证明了神经节苷脂修饰的PEG化脂质体与PEG化脂质体一样具有长循环特性。这些结果表明，用神经节苷脂对聚乙二醇化脂质体进行表面修饰是消除重复注射聚乙二醇化脂质体诱导的ABC现象的一种有前途的策略。ABC现象是开发新型胶体纳米载体的关键问题，因为它们注射后的药代动力学必须在临床环境中重现，以防止意外的副作用并保持药理活性。因此，通过注射聚乙二醇化纳米载体避免诱导抗PEG IgM而不显著损害其体内行为的策略对于未来进一步开发聚乙二醇化纳米载体将是期望的。