Collaborative Research: Unlocking the Potential of Active Lipid Vesicles for Directed Delivery and Controlled Release of Therapeutic Payloads

合作研究：释放活性脂质囊泡用于治疗有效负载的定向递送和受控释放的潜力

• 批准号: 2323046
• 负责人: On Shun Pak
• 金额: $ 23.2万
• 依托单位: Santa Clara University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2323046&HistoricalAwards=false
• 关键词: Collaborative; Research; Unlocking; Potential; Active

Directed delivery and controlled release of therapeutic payloads at targeted locations present substantial opportunities for developing the next generation of therapeutic delivery systems. Lipid vesicles offer a versatile platform to accomplish both functionalities in a compatible and integrated manner. These lipid vesicles are closed structures with a membrane that separates the interior of the vesicle from the outside environment, similar to the membrane of a biological cell. This award will leverage the innate encapsulation capacity of lipid vesicles to enclose both therapeutic payloads and self-propelled particles, enabling the vesicles to undergo directed motion to targeted locations and controlled release of the encapsulated payloads. Successful development of this active vesicle-based drug delivery system will benefit future healthcare. The award will also provide outreach to K-12 students, especially students from underrepresented groups, to enhance public understanding of the challenges and potential biomedical applications of the project. The proposed research fuses emerging developments of self-propelled (or active) particles with newly discovered vesicle responses to light-induced reactions to create an integrated therapeutic delivery system based on lipid vesicles. By combining experimental and theoretical investigations, this award aims to accomplish three specific objectives. The first objective is to examine the motion of lipid vesicles driven internally by encapsulated active particles, realizing the directed delivery of lipid vesicles to targeted locations. Secondly, a non-contact mechanism triggered by photoreactions will be developed to induce the rupture of a vesicle and thereby the rapid release of its encapsulated content. Finally, the functionalities achieved in the aforementioned objectives will be combined in an in-vitro platform to demonstrate directed delivery and controlled release of therapeutics at targeted locations for relevant biomedical applications via the use of active vesicles. Successful completion of this project will advance fundamental understanding of the complex dynamics of lipid vesicles in these non-equilibrium processes, identifying key physical parameters and design principles to guide subsequent developments of active vesicle-based therapeutic delivery systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

治疗有效载荷在靶向位置的定向递送和控制释放为开发下一代治疗递送系统提供了大量机会。脂质囊泡提供了一个多功能的平台，以兼容和整合的方式实现这两种功能。这些脂质囊泡是封闭结构，具有将囊泡内部与外部环境分开的膜，类似于生物细胞的膜。该奖项将利用脂质囊泡的固有封装能力来封装治疗有效载荷和自推进颗粒，使囊泡能够定向运动到目标位置并控制释放封装的有效载荷。这种基于囊泡的主动给药系统的成功开发将有益于未来的医疗保健。该奖项还将为K-12学生，特别是来自代表性不足群体的学生提供外展服务，以提高公众对该项目的挑战和潜在生物医学应用的了解。 拟议的研究融合了自推进（或主动）粒子的新兴发展与新发现的囊泡对光诱导反应的反应，以创建一个基于脂质囊泡的综合治疗递送系统。通过结合实验和理论研究，该奖项旨在实现三个具体目标。第一个目标是检查由封装的活性颗粒内部驱动的脂质囊泡的运动，实现脂质囊泡到靶向位置的定向递送。其次，将开发由光反应触发的非接触机制，以诱导囊泡破裂，从而快速释放其封装的内容物。最后，在上述目标中实现的功能将在体外平台中组合，以证明通过使用活性囊泡在靶向位置处的治疗剂的定向递送和控制释放，用于相关的生物医学应用。该项目的成功完成将促进对脂质囊泡在这些非平衡过程中的复杂动力学的基本理解，确定关键的物理参数和设计原则，以指导基于活性囊泡的治疗递送系统的后续开发。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。