用于刺激敏感型药物纳米载体的pH敏感型聚乙二醇-磷脂共轭物的设计、合成与表征：腙键处取代基对聚乙二醇-磷脂共轭物pH稳定性的影响
Design, synthesis, and characterization of pH-sensitive PEG-PE conjugates for stimuli-sensitive pharmaceutical nanocarriers: the effect of substitutes at the hydrazone linkage on the ph stability of PEG-PE conjugates.
作者信息
Kale Amit A, Torchilin Vladimir P
机构信息
Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts 02115, USA.
出版信息
Bioconjug Chem. 2007 Mar-Apr;18(2):363-70. doi: 10.1021/bc060228x. Epub 2007 Feb 20.
Abstract
A set of aliphatic and aromatic aldehyde-derived hydrazone (HZ)-based acid-sensitive polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugates was synthesized and evaluated for their hydrolytic stability at neutral and slightly acidic pH values. The micelles formed by aliphatic aldehyde-based PEG-HZ-PE conjugates were found to be highly sensitive to mildly acidic pH and reasonably stable at physiologic pH, while those derived from aromatic aldehydes were highly stable at both pH values. The pH-sensitive PEG-PE conjugates with controlled pH sensitivity may find applications in biological stimuli-mediated drug targeting for building pharmaceutical nanocarriers capable of specific release of their cargo at certain pathological sites in the body (tumors, infarcts) or intracellular compartments (endosomes, cytoplasm) demonstrating decreased pH.
摘要
合成了一组基于脂肪族和芳香族醛衍生腙（HZ）的酸敏性聚乙二醇 - 磷脂酰乙醇胺（PEG - PE）共轭物，并评估了它们在中性和略酸性pH值下的水解稳定性。发现由基于脂肪族醛的PEG - HZ - PE共轭物形成的胶束对轻度酸性pH高度敏感，在生理pH下相当稳定，而由芳香族醛衍生的胶束在两种pH值下都高度稳定。具有可控pH敏感性的pH敏感PEG - PE共轭物可能在生物刺激介导的药物靶向中找到应用，用于构建能够在体内某些病理部位（肿瘤、梗死灶）或细胞内区室（内体、细胞质）pH降低时特异性释放其货物的药物纳米载体。
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