Transdermal Delivery by Electroporation and Liposomes

通过电穿孔和脂质体进行透皮递送

• 批准号: 6876701
• 负责人: SEK-WEN HUI
• 金额: $ 39.9万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 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 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6876701
• 关键词: Transdermal; Delivery; Electroporation; Liposomes

EXCEED THE SPACE PROVIDED. Transdermal drug delivery has several potential advantages over other parenteral drug administration methods. Apart from the convenience and non-invasiveness, the skin also provides a "reservoir" that can sustain delivery over a long period. Furthermore, the skin offers multiple sites to avoid local irritation and toxicity, and yet can also offer the option to concentrate drugs at local areas to avoid undesirable systemic effects. However, at present, the clinical use of transdermal delivery is limited by the fact that only small sized drugs can currently be delivered transdermally at a viable rate. The skin forms an efficient barrier for most molecules, and very few non-invasive methods were known to significantly enhance transport through the skin. Our studies have shown that anionic lipids like 1,2-diacyl-sn-3-phosphatidylserine (PS) can very significantly increase the lifetime of the pathways created by electroporation and that this increase in lifetime can be used to delivery the required doses of drugs. Preliminary studies indicate that electroporation in the presence of PS alters the structure of the stratum corneum, the outer most layer of the skin, and also increases its hydration. The modified stratum corneum can allow the passage of larger drugs like insulin. The main aim of this proposal is to use the knowledge that we have gained during the preceding grant period to (a) better define the mechanistic role of anionic lipids in enhancing transdermal transport by electroporation, and (b) to apply this new found knowledge in preclinical studies to deliver drugs that are currently administered by injection. We will investigate the pharmacokinetics and the pharmacodynamics of insulin and two drugs that are used for the treatment of osteoporosis, calcitonin and teriparatide. The results of the proposed study will be a significant first step towards the development of feasible transdermal drug delivery system using anionic lipid enhanced electroporation pathways to deliver therapeutic drugs in clinical trials. PERFORMANCE SITE ========================================Section End===========================================

超出所提供的空间。 与其他肠胃外给药方法相比，透皮给药具有多种潜在优势。除了方便和非侵入性之外，皮肤还提供了一个可以长期维持分娩的“水库”。此外，皮肤提供多个部位以避免局部刺激和毒性，而且还可以提供将药物集中在局部区域以避免不良全身效应的选择。然而，目前透皮递送的临床应用受到以下事实的限制：目前仅小尺寸药物可以以可行的速率透皮递送。皮肤对大多数分子形成有效的屏障，并且已知很少有非侵入性方法能够显着增强通过皮肤的运输。我们的研究表明，阴离子脂质如 1,2-二酰基-sn-3-磷脂酰丝氨酸 (PS) 可以非常显着地延长电穿孔产生的通路的寿命，并且这种寿命的延长可用于输送所需剂量的药物。初步研究表明，PS 存在下的电穿孔会改变皮肤最外层角质层的结构，并增加其水合作用。改良的角质层可以允许较大的药物（如胰岛素）通过。该提案的主要目的是利用我们在之前的资助期内获得的知识来（a）更好地定义阴离子脂质在通过电穿孔增强透皮转运中的机械作用，以及（b）将这些新发现的知识应用于目前通过注射给药的临床前研究。我们将研究胰岛素和两种用于治疗骨质疏松症的药物降钙素和特立帕肽的药代动力学和药效学。拟议研究的结果将是朝着开发可行的透皮药物递送系统迈出的重要的第一步，该系统使用阴离子脂质增强电穿孔途径在临床试验中递送治疗药物。表演网站==========================================部分结束====== =======================================

项目成果

Cyclodextrin enhanced transdermal delivery of piroxicam and carboxyfluorescein by electroporation.

环糊精通过电穿孔增强吡罗昔康和羧基荧光素的透皮递送。

• DOI: 10.1016/j.jconrel.2004.07.026
• 发表时间: 2004
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Murthy,SNarasimha;Zhao,Ya-Li;Sen,Arindam;Hui,SekWen
• 通讯作者: Hui,SekWen

Influence of DMPS on the water retention capacity of electroporated stratum corneum: ATR-FTIR study.

DMPS 对电穿孔角质层保水能力的影响：ATR-FTIR 研究。

• DOI: 10.1016/j.ijpharm.2007.08.031
• 发表时间: 2008
• 期刊: International journal of pharmaceutics
• 影响因子: 5.8
• 作者: Sckolnick,Maria;Hui,Sek-Wen;Sen,Arindam
• 通讯作者: Sen,Arindam

Enhancing transdermal drug delivery with electroporation.

通过电穿孔增强透皮药物递送。

• DOI: 10.2174/187221108783331393
• 发表时间: 2008
• 期刊: Recent patents on drug delivery & formulation
• 作者: Wong,Tak-Wah;Ko,Shu-Fen;Hui,Sek-Wen
• 通讯作者: Hui,Sek-Wen

Electroporation and transcutaneous extraction (ETE) for pharmacokinetic studies of drugs.

用于药物药代动力学研究的电穿孔和经皮提取 (ETE)。

• DOI: 10.1016/j.jconrel.2005.03.012
• 发表时间: 2005
• 期刊: Journal of controlled release : official journal of the Controlled Release Society.
• 作者: Murthy,SNarasimha;Zhao,Ya-Li;Hui,SekWen;Sen,Arindam
• 通讯作者: Sen,Arindam

Induction of cytotoxic T-lymphocytes by electroporation-enhanced needle-free skin immunization.

通过电穿孔增强无针皮肤免疫诱导细胞毒性 T 淋巴细胞。

• DOI: 10.1016/j.vaccine.2005.09.035
• 发表时间: 2006
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Zhao,YL;Murthy,SN;Manjili,MH;Guan,LJ;Sen,A;Hui,SW
• 通讯作者: Hui,SW