Nanoparticle-Stabilized Capsules as Drug Delivery Systems

描述(由申请人提供)： 项目摘要/摘要纳米颗粒稳定胶囊作为药物输送系统纳米颗粒稳定胶囊(NPSC)为制造具有高载体有效载荷比的输送载体提供了一个模块化平台。在最近的研究中，我们开发了一种替代的NPSC稳定模式，该模式依赖于通过纳米颗粒外壳和互补的疏水“油”成分之间的超分子相互作用来稳定胶囊。使用这种方法，我们已经能够生产出直径小到100 nm的纳米胶囊。在我们提出的研究中，我们将基于这种设计制造胶囊，并进行细胞培养研究，以确定其在输送应用中的可行性。我们提出的计划有两个目标：目标1：我们将制造NPSCs，重点是控制胶囊的大小、稳定性和功能化。我们将通过裁剪颗粒-液滴和颗粒-颗粒相互作用来控制颗粒大小和稳定性，并通过环境友好型交联剂稳定NPSC外壳。目的2：随后将在一系列细胞系中确定未交联物和交联物颗粒用于药物输送的有效性。同时，确定有效载荷释放机制，确定药物输送效率。我们还将确定使用叶酸、RGD、半乳糖、转铁蛋白和三苯氧胺靶向的效率。这项为期两年的R21赠款的目标是制定创建纳米级NPSCs的战略，并进行细胞培养研究，展示这些系统的稳定性及其药物输送能力。这些研究将提供概念验证，为未来资助期的动物模型研究奠定基础。 公共卫生相关性： 项目简介：意义：纳米颗粒稳定的胶囊提供了一种将治疗药物输送到体内特定位置(如肿瘤或器官)的新方法。在我们提议的研究中，我们将开发新的策略来制造和调整用于递送应用的颗粒，为获得新的治疗策略提供潜在的途径。

DESCRIPTION (provided by applicant): Project Summary/Abstract Nanoparticle-Stabilized Capsules as Drug Delivery Systems Nanoparticle-stabilized capsules (NPSCs) provide a modular platform for the creation of delivery vehicles featuring a high carrier to payload ratio. In recent research, we have developed an alternative mode of NPSC stabilization that relies on stabilization of the capsule through supramolecular interactions between the nanoparticle shell and complementary hydrophobic "oil" components. Using this method, we have been able to produce nanocapsules featuring diameters as small as 100 nm. In our proposed research we will fabricate capsules based on this design and perform cell culture studies to determine their viability in delivery applications. Our proposed program features two Aims: Aim 1: We will fabricate NPSCs, focusing on the control of capsule size, stability, and functionalization. We will control particle size and stability through tailoring of particle-droplet and particle-particle interactions, as well as stabilize the NPSC shell through environmentally-responsive crosslinking. Aim 2: The efficacy of uncrosslinked and crosslinked particles for drug delivery will then be determined in a range of cell lines. Concurrently, we will determine the mechanism of payload release and determine the efficiency of drug delivery. We will also determine the efficiency of targeting using folate, RGD, galactose, transferrin and tamoxifen targeting. The goal of this two-year R21 grant is to develop strategies for the creation of nanometer-scale NPSCs and perform cell culture studies demonstrating the stability of these systems and their capabilities in drug delivery. These studies will provide proof-of-concept validation that will provide the foundation for animal model studies in future funding periods. PUBLIC HEALTH RELEVANCE: Project Narrative: Significance: Nanoparticle-stabilized capsules present a new means of delivering therapeutics to specific location in the body such as tumors or organs. In our proposed research we will develop new strategies to fabricate and tune particles for delivery applications, providing potential access to new therapeutic strategies.