LIPOSOMES FOR DELIVERY OF COMPOUNDS INTO HAIR FOLLICLES

用于将化合物输送到毛囊中的脂质体

• 批准号: 2517570
• 负责人: LINGNA LI
• 金额: $ 35.55万
• 依托单位: ANTICANCER, INC.
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-19 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2517570
• 关键词: albino mouse; drug delivery systems; gene targeting; hair follicle; liposomes; melanins; method development; monophenol monooxygenase; tissue /cell culture

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.

有一个重要的需要，刺激头发生长的各种 脱发的症状为了达到刺激毛发生长的目的，从生物学上讲- 活性化合物必须在毛囊细胞内递送。活性 原则上化合物也可用于引起毛发的所需变化 颜色和外观。识别这些化合物的最佳方法， 将它们递送到毛囊细胞中的方法是使用适当的 允许研究多种物质的体外系统 一个单独的样本。在凝胶中尤其如此- 支持我们开发的三维组织培养系统 （霍夫曼，R.M. Cancer Cells 3，86-92，1991），其允许完整生长 和测试皮肤的所有成分，包括角质形成细胞、真皮 成纤维细胞和毛囊细胞培养10天或更长时间（Li， L.，等人，Proc. Natl. Acad.科学。- USA. 88，1908-1912，1991）。头发本身 可以在这样的皮肤培养物上生长（Li，L.例如，手稿 制备）。另一方面，已知脂质体-球形 磷脂囊泡与双层膜结构-被认为是 作为细胞内递送不同的 从低分子量药物到DNA质粒。是 在这里提出，使用组织培养系统和荧光标记的 脂质体中包含的化合物，以研究脂质体与 毛囊细胞，以找到细胞结合的最佳组合物， 在给定组成的脂质体中包含不同的低分子量- 重量和高分子量，水溶性和水不溶性 化合物，并找到释放的最佳条件， 脂质体内容物进入毛囊细胞。在II期体外研究中 将进行模型化合物，以确定其对 人类皮肤培养，以开发一个商业系统， 影响毛发生长、颜色和 外观. 建议的商业应用：使用本地状态三维 作为模型小鼠和人皮肤的组织培养系统和脂质体 不同的尺寸和组成作为递送载体，系统可以 开发用于影响头发生长、颜色和外观。