Echogenic Targeted Liposomes: Transfection/Drug Delivery

项目摘要/摘要 识别和治疗动脉疾病的传统手段由于无法指导治疗而受到阻碍。 局部动脉粥样硬化的成分。具有新型超声功能的新型靶向声学传递制剂(脂质体) 交付方法可能会克服这些问题。 脂质体是包裹在水中的磷脂小泡。我们开发了一种独特的 通过工艺和成分使这些脂质体回声的方法。这一公式允许 抗体偶联和治疗性(药物/生物活性气体)掺入的修饰。我们小组的工作已经完成 证明了这些制剂可以将治疗药物整合并输送到细胞，同时保留它们的 回声特性。后者很重要，因为添加治疗性超声波对 这些回声脂质体通过增加细胞递送。 我们的主要目标是开发一种模型载体和一种能够结合治疗药物的技术 在保留治疗剂效果的同时将其输送到靶结构。 我们已经：a)开发了强大的治疗性回声免疫脂质体(ELIP)；b)开发了超声波 载药Elip的治疗参数和c)决定了我们治疗Elip的疗效 减缓/稳定动脉粥样硬化的进展。 我们现在将把我们的发现转化为用于不稳定动脉粥样硬化，并将它们转化为临床环境。 我们将开发一种新的超声方法，用于将治疗性药物输送到冠状动脉床上。我们会 通过体内超声激活评估我们的治疗载体，并将我们的最佳策略转化为 临床环境。 这些试剂和技术的发展将对癌症的治疗产生深远的影响。 慢性高危动脉粥样硬化。

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.