Liposome targeting of high molecular weight DNA to the hair follicles of histocultured skin: a model for gene therapy of the hair growth processes.
Liposome targeting of high molecular weight DNA to the hair follicles of histocultured skin: a model for gene therapy of the hair growth processes.
复制标题
将高分子量 DNA 靶向组织培养皮肤毛囊的脂质体：毛发生长过程基因治疗的模型。
DOI：
10.1007/bf02633949
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发表时间：
1993
期刊：
影响因子：
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通讯作者：
Hoffman,RM
中科院分区：
文献类型：
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作者：
Li,L;Lishko,V;Hoffman,RM
尊敬的编辑：在海绵凝胶基质上的完整皮肤的组织培养为组织工程和皮肤固有的重要过程如毛发生长和对各种试剂的毒性的体外研究提供了许多机会（Li等人，1991年，1992年a，1992年b）。对于用于透皮药物递送和影响毛发本身的活性化合物的递送的毛发-毛囊（附属物）途径，存在越来越多的兴趣。Feldmann和Maibach（1967）和Maibach（1971）指出，各种试验化合物的体外吸收取决于所用人体皮肤形态的区域差异。在毛囊密度和大小增加的区域吸收增加，例如前额和头皮。最近，Illel等人。（1991）报道，相对于无附件（无毛囊）皮肤，在正常的含附件、无毛大鼠皮肤（毛囊密度10-200/cm 2）中，代表性促渗剂的体外经皮稳态通量高2-4倍。文献中的其他报道也表明通过毛囊皮脂腺器的显著量的渗透（Bidmon等人，1990; Rutherford等人，1969; Suzuki等人，1978年）。脂质体已被广泛并成功地用作递送系统，将通常不能穿过质膜的大分子物质转运到细胞中（Gregoriadis 1984，1988; Egbaria和Weiner，1990）。我们最近报道了钙黄绿素染料包埋的脂质体特异性靶向组织培养的完整皮肤中的毛囊（Li等人，1992年d）。我们的研究结果得到了Lieb等人的有力证实。（1992），证明脂质体制剂比任何其他测试的载体更有效地通过毛囊途径用仓鼠耳模型将羧基荧光素递送到毛囊皮脂腺单位中。然后，我们开发了脂质体介导的黑色素靶向递送到组织培养的白发小鼠皮肤中的毛囊和毛干本身中（Li等人，1993年）。这些研究具有许多分支，包括靶向毛发生长修饰和跨毛囊经皮递送系统。多年前，我们开发了将DNA包埋在脂质体中的技术（霍夫曼等人，1978年）。我们在这里报道的研究中利用DNA脂质体将高分子量DNA靶向毛囊本身作为毛发生长过程的基因治疗模型。
Dear Editor: The histoculture of intact skin on sponge-gel matrices offers many opportunities for tissue engineering and the in vitro study of important processes intrinsic to skin such as hair growth and toxicity to various agents (Li et al., 1991, 1992a, 1992b). There is an increasing interest in the hair-follicular (appendage) route for delivery of drugs for both trans-dermal drug delivery and delivery of active compounds affecting hair itself. Feldmann and Maibach (1967) and Maibach (1971) noted that in vitro absorption of various compounds tested depended upon the regional difference in the morphology of human skin used. Absorption was increased in areas of increased follicular density and size, eg forehead and scalp. Recently, Illel et al.(1991) reported that the in vitro percutaneous steady-state flux for representative penetrants was 2-4 times higher in normal appendage-containing, hairless rat skin (follicular density 10-200/cm2) relative to their appendage-free (follicle-free) skin. Other reports in the literature also suggested significant amount of penetration via the pilosebaceous apparatus (Bidmon et al., 1990; Rutherford et al., 1969; Suzuki et al., 1978). Liposomes have been widely and successfully used as delivery systems to transport macromolecular substances into the cell which can not normally cross the plasma membrane (Gregoriadis 1984, 1988; Egbaria and Weiner, 1990). We have recently reported that calcein-dye entrapped liposomes specifically targeted hair follicles in histocultured intact skin (Li et al., 1992d). Our results were strongly confirmed by studies by Lieb et al.(1992) demonstrating that liposomal formulations were more efficient than any other vehicle tested for delivery of carboxyfluorescein through the follicular route into the pilosebaceous units with the hamster ear model. We then developed liposome-mediated targeted delivery of melanin into hair follicles and the hair shaft itself in histocultured white-haired mouse skin (Li et al., 1993). These studies have many ramifications including targeted hair growth modification and trans-follicular transdermal delivery systems.A number of years ago we developed the technique of entrapping DNA in liposomes (Hoffman et al., 1978). We have utilized DNA liposomes in the studies reported here to target high molecular weight DNA to the hair follicle itself as a model of gene therapy of the hair growth processes.