Ise Mamiko, Ise Hirohiko, Shiba Yuji, Kobayashi Satoshi, Goto Mitsuaki, Takahashi Masafumi, Akaike Toshihiro, Ikeda Uichi
Division of Cardiovascular Sciences, Department of Organ Regeneration, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
J Artif Organs. 2011 Dec;14(4):301-9. doi: 10.1007/s10047-011-0595-3. Epub 2011 Aug 2.
The targeted delivery of anti-inflammatory agents has great therapeutic potential for treating restenosis following percutaneous coronary intervention. To develop a drug delivery system targeted to injured blood vessels, we examined whether N-acetylglucosamine (GlcNAc)-bearing polymer-coated liposomes (GlcNAc-Ls) are specifically taken up by vascular smooth muscle cells (VSMCs). Flow cytometric analysis revealed that GlcNAc-Ls were taken up by VSMCs in vitro. Furthermore, GlcNAc-Ls were intravenously administered to mice that had undergone wire-mediated vascular injury. GlcNAc-Ls markedly accumulated at the intramural site of the injured vessel walls but not at the contralateral (uninjured) vessel walls. These results demonstrated that GlcNAc-Ls can be specifically taken up by VSMCs both in vitro and in vivo. We propose a novel strategy of using GlcNAc-Ls that has potential for application in drug delivery targeted to injured blood vessels.
抗炎药物的靶向递送在经皮冠状动脉介入治疗后再狭窄的治疗中具有巨大的治疗潜力。为了开发一种靶向损伤血管的药物递送系统，我们研究了携带N-乙酰葡萄糖胺（GlcNAc）的聚合物包被脂质体（GlcNAc-Ls）是否能被血管平滑肌细胞（VSMCs）特异性摄取。流式细胞术分析显示，GlcNAc-Ls在体外能被VSMCs摄取。此外，将GlcNAc-Ls静脉注射到经钢丝介导血管损伤的小鼠体内。GlcNAc-Ls在损伤血管壁的壁内部位显著蓄积，而在对侧（未损伤）血管壁则无蓄积。这些结果表明，GlcNAc-Ls在体外和体内均可被VSMCs特异性摄取。我们提出了一种使用GlcNAc-Ls的新策略，该策略在靶向损伤血管的药物递送中具有应用潜力。
