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Gene delivery to hair follicles by multifunctional envelope-type nano device

通过多功能信封型纳米装置将基因递送至毛囊

基本信息

批准号：
18590134
负责人：
KOGURE Kentaro
金额：
$ 2.49万
依托单位：
Kyoto Pharmaceutical University (2007)Hokkaido University (2006)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590134/
关键词：
gene delivery hair follicules gene delivery system

项目摘要

Head investigator of this project tried to develop novel gene delivery system to hair follicles of mice by topical application of non-viral gene delivery system octaarginine-modified multifunctional envelope-type nano device (R8-MEND). After treatment of mice back skin with the R8-MEND containing EGFP-encoding plasmid DNA or LacZ-encoding plasmid DNA, expression of EGFP protein and beta-gal positive staining image were observed in cross section of the skin treated with R8-MEND. Moreover, topical application of R8-MEND, which contained Bone morphogenetic protein type IA receptor (BMPRIA) -encoding plasmid DNA, was performed to back skin of 4 weeks old ICR mice. After 2 weeks of the treatment, position of hair follicles in the skin was almost the same as before treatment, although position of hair follicles of control mice was moved to upper region because of progress of hair cycle. It is suggested that topical application of R8-MEND-BMPRIA prolonged hair cycle. Then, head investigator t … More ried to inhibit the specific genes relating to growth and cycle of hair by delivery of siRNA against those genes via topical application of R8-MEND. However, no significant effect was observed. To know the reason why the siRNA delivery by R8-MEND was not effective, head investigator observed cross section of the skin treated by R8-MEND containing siRNA labeled with rhodamine. As a result, very a few siRNA was observed in the skin, indicating that improvement of siRNA delivery is necessary. Then, head investigator tried to delivery liposomes, which are the model of MEND, via iontophoresis. Head investigator found optimal size (>400nm) and surface charge (positive) of liposomes for transfollicular delivery of nano-particles via iontophoresis. Moreover, head investigator succeeded in transfollicular delivery of liposomes containing model drug solution (aqueous rhodamine) into skin via iontophoresis in vivo. Therefore, the delivery of R8-MEND containing siRNA should be achieved by this novel transfolicular delivery system in near future. Less

本项目的主要研究者试图通过局部应用非病毒基因递送系统辛托品修饰的多功能纳米装置（R8-MEND）来开发新型的小鼠毛囊基因递送系统。用含有EGFP编码质粒DNA或LacZ编码质粒DNA的R8-MEND处理小鼠背部皮肤后，在用R8-MEND处理的皮肤横截面中观察到EGFP蛋白的表达和β-gal阳性染色图像。此外，将含有骨形态发生蛋白IA型受体（BMPRIA）编码质粒DNA的R8-MEND局部应用于4周龄ICR小鼠的背部皮肤。治疗2周后，皮肤中毛囊的位置几乎与治疗前相同，尽管对照小鼠的毛囊位置由于毛发周期的进展而移动到上部区域。提示局部应用R8-MEND-BMPRIA可延长毛发周期。然后，首席调查员t ...更多信息试图通过局部应用R8-MEND递送针对这些基因的siRNA来抑制与毛发生长和周期相关的特定基因。然而，未观察到显著效果。为了了解R8-MEND的siRNA递送无效的原因，首席研究员观察了用含有罗丹明标记的siRNA的R8-MEND处理的皮肤的横截面。结果，在皮肤中观察到非常少的siRNA，表明siRNA递送的改善是必要的。然后，首席研究员尝试通过离子电渗法递送脂质体，这是MEND的模型。首席研究员发现脂质体的最佳尺寸（> 400 nm）和表面电荷（正），用于通过离子电渗法跨卵泡递送纳米颗粒。此外，首席研究员成功地通过体内离子电渗法将含有模型药物溶液（罗丹明水溶液）的脂质体透毛囊递送到皮肤中。因此，在不久的将来，R8-MEND的siRNA的递送将通过这种新的经滤泡递送系统实现。少