Exploring Controlled Drug Release from Magneto-Liposomes using Ultrsound Generation by High Frequency Pulsed Magnetic Fields.

拟议的工作研究了如何利用微小磁性颗粒和磁场组合产生的声波来提供小药物分子的有效递送。 与现有技术相比，这种实验方法有可能以非常快的方式在人体深处执行任务。该研究的目的是探索控制这种拟议药物输送方法有效性的精确基础物理和化学，并推动其极限，以便能够设计出实用的医疗设备。在这项工作中，将解决可以产生多少这种超声以及如何放置磁性颗粒以实现有效的药物输送的问题。拟议的工作将提供独特的培训机会，本科生和研究生的研究助理在化学，物理学和医学科学的多学科领域的理论和实验工具。拟议的研究的主要目标是评估一种新的改进的磁脂质体结构的药物递送能力，该结构旨在解决以前磁脂质体设计的缺点。在这种新的磁性脂质体结构中，金包覆的氧化铁纳米颗粒将用作超声源，用于触发脂质体中的药物递送。磁性颗粒的金表面促进化学连接剂经由硫醇官能团的强附着。产生局部超声振动的磁性结构通过胆固醇和磷脂的硫醇化聚乙二醇衍生物附着于脂质体。作为拟议研究的次要目标，PI旨在探索在旋转磁场中从非球形磁性纳米棒产生潜在更有效的超声过程。该提案描述了一种能够机械转动胶体纳米结构的脉冲磁体。一个粗粒度的分子动力学模拟将被开发，以提供物理洞察超声波产生的机制，在胶体磁性解决方案。最近发现，胶体磁性纳米结构能够产生足够大的量的超声，可以诱导磁脂质体中的药物从高频磁场释放。关键的假设是，一旦磁性颗粒移动到脂质体结构之外，就可以触发更有效的药物释放，并且与以前的设计相比，可以从相同尺寸的磁脂质体携带更大的药物递送能力。预期来自脂质体的药物分子可以在非常短的时间（亚毫秒时间尺度）内释放而没有显著的温度升高，这将为短寿命温度敏感性药物分子的实际递送创造新的平台。与以前的发现相比，拟议的工作还以不同的方式解决了超声波产生问题。据推测，超声波可以产生从各向异性磁性纳米结构（纳米棒）更有效地在旋转磁场比从球形磁性颗粒在不均匀的非旋转磁场。

The proposed work investigates how sound waves from the combination of tiny magnetic particles and magnetic fields can be utilized to provide efficient delivery of small drug molecules. This experimental approach has a potential to carry out task deep inside the human body in a very fast manner compared to existing technology. The objective of the research is to explore the precise underlying physics and chemistry that controls the effectiveness of this proposed drug delivery methodology and push its limits to be able to engineer a practical medical device. How much of this ultrasound can be generated and how the magnetic particles need to be placed for effective drug delivery will be addressed in this work. The proposed work will provide unique training opportunity to undergraduate and graduate research assistants in theoretical and experimental tools of multidisciplinary fields of chemistry, physics, and medical sciences. The key objective of the proposed research is to assess the drug delivery capability of a new improved magneto-liposome structure that aims at addressing the shortcomings of previous magneto liposome designs. In this new magnetic liposome structure, gold coated iron oxide nanoparticles will be used as a source of ultrasound for triggering drug delivery in the liposomes. The gold surface of the magnetic particles facilitates a strong attachment of chemical linker via thiol functional groups. The magnetic structures that produce local ultrasonic vibrations are attached to the liposomes via thiolated polyethylene glycol derivatives of cholesterol and phospholipids. As a secondary objective of the proposed research, the PI aims at exploring a potentially more efficient ultrasound generation process from non-spherical magnetic nanorods in rotating magnetic fields. The proposal describes a pulsed magnet capable of mechanically turning colloidal nanostructures. A course-grained molecular dynamics simulation will be developed to provide physical insight into the mechanism of ultrasound generation in colloidal magnetic solutions. It has been found recently that colloidal magnetic nanostructures are able to produce sufficiently large amount of ultrasound that can induce drug release in magneto liposomes from high frequency magnetic fields. The key hypothesis is that once the magnetic particles are moved outside the liposomes structures, one can trigger more efficient drug release, and can carry larger drug delivery capacity from the same sized magneto liposomes when compared to previous designs. It is anticipated that the drug molecules from the liposomes can be released in a very short time (sub millisecond timescale) without significant temperature rise, which will create a new platform for practical delivery of short lived temperature sensitive drug molecules. The proposed work also addresses ultrasound generation in different ways compared to the previous discoveries. It is hypothesized that ultrasound may be generated from anisotropic magnetic nanostructures (nanorods) more effectively in rotating magnetic fields than from spherical magnetic particles in inhomogeneous non-rotating magnetic fields.