TRANSDERMAL DELIVERY BY ELECTROPORATION AND LIPOSOMES

通过电穿孔和脂质体进行透皮递送

• 批准号: 2464828
• 负责人: SEK-WEN HUI
• 金额: $ 19.96万
• 依托单位: ROSWELL PARK CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2464828
• 关键词: animal tissue; clinical research; electrodes; electroporation; gene therapy; hair follicle; human tissue; laboratory mouse; liposomes; method development; neoplasm /cancer photoradiation therapy; skin; skin absorption; skin pharmacology; swine; transdermal drug delivery

DESCRIPTION: Dr. Hui and his group propose to develop transdermal delivery methods based on recent advances in electroporation and liposome technologies. Their long range goal is to develop convenient, safe, and effective methodologies that can be applied to introduce drugs and genes across the skin barrier, for the purpose of gene therapy, controlled drug release, and topical treatment of local ailments including skin carcinoma. The stratum corneum (SC), the top layer of skin, is the major barrier of transdermal transport, and contributes to most of the electrical resistance of the skin. Electroporation of the SC enhances the transdermal transport by several orders of magnitude. It is proposed to use prior knowledge and experience of Dr. Hui's group in cell electroporation to broaden understanding of the skin electroporation mechanism, and to use this as a basis to devise efficient electroporation protcols for transdermal delivery. It is proposed to study the changes in ultrastructure, electrical impedance, and molecular transport through the skin by electric pulses, using surface electrodes on the whole skin. Liposomes have been found to preferentially partition into hair follicles, which offer another route of transdermal transport. It is proposed to investigate the mechanism of liposome-mediated transdermal transport, in order to utilize liposomes to enhance transdermal delivery, alone or in association with electroporation. In particular, charged liposomes will be utilized as carriers of DNA or uncharged molecules, for the purpose of drug and gene transfer. In feasibility studies, it is proposed to apply electroporation and/or liposome methods to deliver photodynamic therapy (PDT) drugs through excised porcine skin, live murine skin, and biopsied human skin with multiple basal cell carcinomas or squamous cell carcinomas, to enhance localized drug delivery for PDT. As a model for gene delivery, it is proposed to apply these methods to deliver plasmids coding for tyrosinase to transfect mutant melanocytes in mice, to establish an assay for platelet storage pool deficiency gene products.

描述：许博士及其团队提议开发透皮给药 基于电穿孔和脂质体最新进展的方法 技术。 他们的长远目标是开发便捷、安全、 可用于引入药物和基因的有效方法 跨越皮肤屏障，用于基因治疗、受控药物 释放和局部治疗局部疾病，包括皮肤癌。 角质层（SC）是皮肤的最顶层，是皮肤的主要屏障。 透皮运输，并贡献大部分电阻 皮肤的。 SC 的电穿孔增强了透皮运输 提高了几个数量级。 建议利用先验知识和 惠博士课题组在细胞电穿孔方面的经验拓宽 了解皮肤电穿孔机制，并将其用作 为设计用于透皮递送的有效电穿孔方案奠定了基础。 建议研究超微结构、电阻抗、 以及利用表面通过电脉冲通过皮肤进行分子运输 整个皮肤上的电极。 人们发现脂质体优先分配到毛囊中， 这提供了另一种透皮运输途径。 建议 研究脂质体介导的透皮转运机制 为了利用脂质体来增强透皮递送，单独或联合使用 与电穿孔的关联。 特别是，带电脂质体将 用作 DNA 或不带电分子的载体，用于药物用途 和基因转移。 在可行性研究中，建议应用电穿孔和/或 脂质体方法通过切除递送光动力治疗（PDT）药物 猪皮肤、活体鼠皮肤和具有多种基底层的活检人体皮肤 细胞癌或鳞状细胞癌，增强局部药物 PDT 交付。 作为基因传递的模型，建议应用 这些方法可传递编码酪氨酸酶的质粒以转染突变体 小鼠黑素细胞，建立血小板储存池测定方法 缺陷基因产物。