Myristic acid-conjugated polyethylenimine for brain-targeting delivery: in vivo and ex vivo imaging evaluation
Myristic acid-conjugated polyethylenimine for brain-targeting delivery: in vivo and ex vivo imaging evaluation
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DOI：
10.3109/10611860903494229
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发表时间：
2010-07-01
影响因子：
4.5
通讯作者：
Lu, Weiyue
中科院分区：
文献类型：
--
作者：
Meng, Qinggang;Yu, Mei;Lu, Weiyue
为了研究肉豆蔻酸（MC）介导聚乙烯亚胺（PEI）脑内基因传递的潜力，合成了MC与PEI的共价偶联物（MC-PEI）。将近红外荧光探针IR 820缀合至MC-PEI以探索其在静脉内（i. v.）在小鼠中施用。采用近红外荧光成像技术评价MC-PEI的脑靶向性，并通过荧光强度半定量分析MC-PEI的脑靶向性。静脉内给药后12小时，在脑中检测到显著的NIR荧光信号，并通过全脑和脑切片成像进一步证实。荧光强度的半定量结果进一步支持MC-PEI的成功脑递送，与未修饰的PEI相比，这导致静脉注射后脑摄取的非常显著的增加（类似于200%）。使用琼脂糖凝胶阻滞测定进一步证实MC-PEI浓缩DNA的能力，表明其用于基因递送的潜力。显著的体内和离体结果表明MC-PEI是一种很有前途的脑靶向药物递送系统，特别是用于基因递送。
To investigate the potential of myristic acid (MC) to mediate brain delivery of polyethylenimine (PEI) as a gene delivery system, a covalent conjugate (MC-PEI) of MC, and PEI was synthesized. A near-infrared fluorescence probe, IR820 was conjugated to MC-PEI to explore its in vivo distribution after intravenous (i.v.) administration in mice. The brain targeting ability of MC-PEI was evaluated by near-infrared fluorescence imaging and analyzed semiquantitatively by fluorescence intensity, respectively. Significant NIR fluorescent signal was detected in the brain 12 h after i.v. administration and further confirmed by imaging the whole brain and brain slices. Semiquantitative results from fluorescence intensity further supported the successful brain delivery of MC-PEI which led to a very significant increase (similar to 200%) in the brain uptake after i.v. injection in comparison with unmodified PEI. The capability of MC-PEI to condense DNA was further confirmed using agarose gel retardation assay, indicating its potential for gene delivery. The significant in vivo and ex vivo results suggest that MC-PEI is a promising brain-targeting drug delivery system, especially for gene delivery.