Clinical Evaluation of Novel Methods for Extending Microneedle Pore Lifetime

延长微针孔隙寿命新方法的临床评价

基本信息

批准号：
8003639
负责人：
Nicole K Brogden
金额：
$ 3.23万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8003639
关键词：
Alcohol abuse Alcoholism Animal Model Biological Products Biomedical Engineering Cavia Cell Culture Techniques Clinical Development Diclofenac Drug Formulations Drug Kinetics Family suidae Goals Healed Heroin Abuse Human In Vitro Knowledge Lead Medical Methods Modeling Naltrexone Narcotic Antagonists Opiate Addiction Opioid Oral Pain Pathway interactions Pharmaceutical Preparations Process Prostaglandin-Endoperoxide Synthase Public Health Research Research Methodology Research Project Grants Research Training Skin Small Interfering RNA Solid Stainless Steel Techniques Time Topical application Transdermal substance administration Vascular Endothelial Growth Factors Work Wound Healing alcoholism therapy celecoxib clinical application clinically relevant healing improved in vivo Model innovation novel patient safety public health relevance research clinical testing

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of the proposed research project entitled "Clinical evaluation of novel methods for extending microneedle pore lifetime" is to improve current methods of transdermal drug delivery by increasing the lifetime of pores created from inserting microneedles into the skin. Improvement of transdermal drug delivery techniques (via the use of microneedles) would have important clinical implications by providing a less invasive means to deliver drugs systemically, which would lead to greater patient safety and compliance. This could also have strong implications in developing better treatments for alcoholism and opiate addiction, as this proposal examines the delivery of naltrexone (an opiate antagonist used for the treatment of opioid and alcohol abuse) following microneedle insertion. Effective transdermal delivery would be an excellent alternative to the current oral and parenteral formulations of naltrexone. The specific aims of the proposal include 1) inhibition of the cyclooxygenase (COX) pathway as a means to inhibit pore closure, 2) pharmacokinetic analysis of naltrexone to characterize pore lifetime following COX inhibition, and 3) employing small-interfering RNA (siRNA) methods to inhibit pore closure. The research methods will involve the use of in vitro and in vivo models (cell culture, qRT-PCR, ELISAs), animal models (hairless guinea pigs and Yucatan miniature pigs), and human studies. Many of the methods described in the proposal involve novel applications of commercially available products, or development of innovative means to improve transdermal drug delivery with the use of microneedles. Studying these compounds and delivery methods makes it feasible to do translational bioengineering and biopharmaceutical training research in human proof-of-concept studies.

描述（由申请人提供）：题为“延长微针毛孔寿命的新方法的临床评估”的拟议研究项目的长期目标是通过增加将微针插入所产生的毛孔的寿命来改进现有的透皮药物递送方法。皮肤。透皮给药技术的改进（通过使用微针）将通过提供一种侵入性较小的全身给药方式而具有重要的临床意义，这将提高患者的安全性和依从性。这也可能对开发更好的酗酒和阿片成瘾治疗方法产生重大影响，因为该提案检查了微针插入后纳曲酮（一种用于治疗阿片类药物和酒精滥用的阿片拮抗剂）的输送。有效的透皮给药将是目前纳曲酮口服和肠胃外制剂的绝佳替代品。该提案的具体目标包括 1) 抑制环氧合酶 (COX) 途径，作为抑制毛孔闭合的手段，2) 纳曲酮的药代动力学分析，以表征 COX 抑制后的毛孔寿命，以及 3) 采用小干扰 RNA (siRNA)抑制毛孔闭合的方法。研究方法将涉及使用体外和体内模型（细胞培养、qRT-PCR、ELISA）、动物模型（无毛豚鼠和尤卡坦小型猪）和人体研究。该提案中描述的许多方法涉及市售产品的新颖应用，或开发创新手段以使用微针改善透皮药物输送。研究这些化合物和递送方法使得在人体概念验证研究中进行转化生物工程和生物制药培训研究成为可能。