LIPOSOMES FOR DELIVERY OF COMPOUNDS INTO HAIR FOLLICLES

对于不同的人来说，刺激头发生长是一个重要的需要 脱发的情况。为了实现毛发生长刺激，从生物学上讲- 活性化合物必须被输送到毛囊细胞内。主动型 原则上，化合物也可以用来引起所需的头发变化。 颜色和外观。鉴定这类化合物的最佳方法和 将它们输送到毛囊细胞的方法是使用适当的 允许研究多种物质的体外系统 在单个标本上。在凝胶中尤其如此- 我们开发的支持式三维组织培养系统 (霍夫曼，R.M.癌细胞3，86-92,1991)，允许完整的生长 以及检测皮肤的所有成分，包括角质形成细胞、真皮 成纤维细胞和毛囊细胞，持续10天或更长时间(Li， L.，等人。程序娜塔莉。阿卡德。科学--美国，88,1908-1912,1991)头发本身 可以在这种皮肤培养物上生长(Li，L.等人，手稿in 准备)。另一方面，众所周知，脂质体-球形 具有双层膜结构的磷脂小泡被考虑 作为细胞内传递不同物质的便捷手段 物质--从低分子药物到DNA质粒。它是 在这里提出，使用组织培养系统和荧光标记 脂质体中包含的化合物，以研究脂质体与 毛囊细胞，为了找到细胞结合的最佳成分， 在给定成分的脂质体中加入不同的低分子- 重量与高分子量、水溶与水不溶 并找出释放的最佳条件。 脂质体中的物质进入毛囊细胞。在第二阶段，体外研究 将用模型化合物来确定它们对 人类皮肤培养，以开发一种商业系统，用于内部 影响头发生长、颜色和颜色的物质的毛囊输送 外表。 建议的商业应用：使用原生状态三维 以小鼠和人皮肤为模型的组织培养体系及其脂质体 作为不同大小和组成的运输工具，一个系统可以 专为影响头发生长、颜色和外观而开发。

There is an important need to stimulate hair growth for various conditions of alopecia. To achieve hair growth stimulation,biologically- active compounds must be delivered inside hair-follicle cells. Active compounds in principle can be also used to cause desired changes in hair color and appearance. The optimal way to identify such compounds and methods of their delivery into hair-follicle cells is to use appropriate in vitro systems which allow the study of a large variety of substances on an individual specimen. This is particularly the case in the gel- supported three-dimensional histoculture system we have developed (Hoffman, R.M. Cancer Cells 3, 86-92, 1991) that allows the intact growth and testing of all components of skin, including keratinocytes, dermal fibroblasts and hair-follicle cells, for a period of 10 days or more (Li, L., et al. Proc. Natl. Acad. Sci.-USA. 88, 1908-1912, 1991). Hair itself can grow on such skin cultures (Li, L. et al., manuscript in preparation). On the other hand, it is known that liposomes - spherical phospholipid vesicles with bilayer membrane structure - are considered as convenient means for the intracellular delivery of different substances - from low-molecular-weight drugs to DNA plasmids. It is proposed here, using the histoculture system and fluorescent-labeled compounds included into liposomes, to study liposome interactions with hair-follicle cells, to find the optimal compositions for cell binding, to include into liposomes of a given composition different low-molecular- weight and high-molecular-weight, water-soluble and water-insoluble compounds and to find the optimal conditions for the release of the liposomal content into hair-follicle cells. In Phase II, in vitro studies with model compounds will be performed to determine their effects on human skin culture in order to develop a commercial system for intra- follicle delivery of substances influencing hair growth, color and appearance. PROPOSED COMMERCIAL APPLICATION: Using native-state three-dimensional histoculture system of mouse and human skin as a model and liposomes of different size and composition as delivery vehicles, a system can be developed for influencing hair growth, color and appearance.