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

• 批准号: 8146894
• 负责人: Nicole K Brogden
• 金额: $ 3.32万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 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/8146894
• 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; 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; compliance behavior; healing; improved; in vivo Model; innovation; novel; opioid abuse; patient safety; public health relevance; research clinical testing

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“延长微针孔寿命新方法的临床评估”的拟议研究项目的长期目标是通过增加将微针插入皮肤所产生的孔的寿命来改进目前的透皮给药方法。改进经皮给药技术（通过使用微针）将具有重要的临床意义，因为它提供了一种侵入性较小的全身给药方法，这将提高患者的安全性和依从性。这也可能对开发更好的治疗酒精中毒和阿片类药物成瘾的方法有很大的影响，因为本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类拮抗剂）的递送。有效的透皮给药将是目前口服和静脉注射纳曲酮制剂的一个极好的替代方案。该提案的具体目标包括1)抑制环氧化酶（COX）途径作为抑制孔关闭的手段，2)纳曲酮的药代动力学分析以表征COX抑制后的孔寿命，以及3)采用小干扰RNA （siRNA）方法抑制孔关闭。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（无毛豚鼠和尤卡坦迷你猪）和人体研究。提案中描述的许多方法涉及对市售产品的新应用，或开发创新手段，以使用微针改善经皮给药。研究这些化合物和给药方法使得在人类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。