Echogenic Targeted Liposomes: Transfection/Drug Delivery

回声靶向脂质体：转染/药物递送

• 批准号: 9217206
• 负责人: David D McPherson
• 金额: $ 75.72万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9217206
• 关键词: Acoustics; Aftercare; Animals; Antibodies; Area; Arterial Fatty Streak; Atherosclerosis; Beds; Cardiovascular system; Carotid stent; Cells; Chronic; Clinical; Clinical Trials; Computer Simulation; Coronary; Coronary Arteriosclerosis; Coronary artery; Data; Development; Devices; Disease; Drug Delivery Systems; Elements; Encapsulated; Family suidae; Formulation; Gases; Goals; Health Sciences; Histologic; Human; Hyperplasia; Image; Immunoliposome; In Vitro; Inflammation; Intercellular adhesion molecule 1; Intervention; Investigation; Investigational Drugs; Knowledge; Laboratories; Life; Liposomes; Mechanics; Mediating; Methodology; Methods; Modeling; Modification; Monitor; Nitric Oxide; Patients; Pharmaceutical Preparations; Pharmacology; Phase; Phospholipids; Physiologic pulse; Physiological; Positron-Emission Tomography; Preparation; Process; Property; Protocols documentation; Randomized; Research; Safety; Site; Stents; Structure; Techniques; Texas; Therapeutic; Therapeutic Effect; Time; Transducers; Transfection; Translating; Translations; Ultrasonic Transducer; Ultrasonography; Universities; Vesicle; Work; X-Ray Computed Tomography; aqueous; chest computed tomography; high risk; human study; image guided; imaging modality; improved; in vivo; novel; novel therapeutics; primary outcome; prototype; research clinical testing; restenosis; rosiglitazone

PROJECT SUMMARY/ABSTRACT Traditional means to identify and treat arterial disease are hampered by their inability to direct therapeutics to local atheroma components. Novel targeted acoustic delivery agents (liposomes) with novel ultrasound delivery methodologies may overcome these problems. Liposomes are phospholipid vesicles enclosing an aqueous space. We have developed a unique methodology that, by process and composition, makes these liposomes echogenic. This formulation allows modification for antibody conjugation and therapeutic (drug/bioactive gas) incorporation. Work by our group has demonstrated that these formulations can incorporate and deliver therapeutics to cells, while retaining their echogenic properties. The latter is important as the addition of therapeutic ultrasound has a unique effect on these echogenic liposomes by increasing cellular delivery. Our principal aim is to develop a model carrier and a technique that has the ability to incorporate a therapeutic with delivery to a target structure while retaining the therapeutic’s effects. We have: a) developed robust therapeutic echogenic immunoliposomes (ELIP); b) developed ultrasound parameters for therapeutic delivery of loaded ELIP and c) determined the efficacy of our therapeutic ELIP in slowing/stabilizing atheroma progression. We will now translate our discoveries for use in unstable atheroma and translate them into the clinical setting. We will develop a novel ultrasound methodology for therapeutic delivery into the coronary arterial beds. We will evaluate our therapeutic-loaded carriers with ultrasound activation in vivo and translate our optimal strategy into the clinical setting. Development of these agents and techniques would have far reaching implications for the treatment of chronic high risk atherosclerosis.

项目总结/摘要 识别和治疗动脉疾病的传统方法因无法指导治疗而受到阻碍 局部动脉粥样硬化成分。具有新型超声的新型靶向声学递送剂（脂质体） 交付方法可以克服这些问题。 脂质体是包封水性空间的磷脂囊泡。我们开发了一种独特的 通过工艺和组合物使这些脂质体产生回声的方法。该配方允许 用于抗体缀合和治疗性（药物/生物活性气体）掺入的修饰。我们小组的工作 证明这些制剂可以掺入治疗剂并将其递送至细胞，同时保留它们的生物活性。 回声特性后者是重要的，因为治疗性超声的添加对 这些回声脂质体通过增加细胞输送。 我们的主要目标是开发一种模型载体和一种能够将治疗药物 在保持治疗效果的同时递送到靶结构。 我们已经：a）开发了强大的治疗回声免疫脂质体（ELIP）; B）开发了超声 c）确定我们的治疗性ELIP在治疗性递送负载ELIP中的功效， 减缓/稳定动脉粥样硬化进展。 我们现在将把我们的发现用于不稳定的动脉粥样硬化，并将其转化为临床环境。 我们将开发一种新的超声方法用于冠状动脉床的治疗。我们将 通过体内超声激活评估我们的治疗负载载体，并将我们的最佳策略转化为 临床设置。 这些药物和技术的发展将对治疗 慢性高危动脉粥样硬化