Nanoparticle-Stabilized Capsules as Drug Delivery Systems

描述（由申请人提供）： 纳米颗粒稳定的胶囊作为药物递送系统纳米颗粒稳定的胶囊（NPSC）提供了一个模块化平台，用于创建具有高载体有效载荷比的递送载体。在最近的研究中，我们已经开发了NPSC稳定的替代模式，其依赖于通过纳米颗粒壳和互补的疏水“油”组分之间的超分子相互作用来稳定胶囊。使用这种方法，我们已经能够生产直径小至100 nm的纳米胶囊。在我们提出的研究中，我们将根据这种设计制造胶囊，并进行细胞培养研究，以确定它们在递送应用中的可行性。我们提出的计划有两个目标：目标1：我们将制造NPSC，专注于控制胶囊的大小，稳定性和功能化。我们将通过调整颗粒-液滴和颗粒-颗粒相互作用来控制颗粒尺寸和稳定性，并通过环境响应交联来稳定NPSC壳。目的2：然后将在一系列细胞系中确定用于药物递送的未交联和交联颗粒的功效。同时，我们将确定有效载荷释放的机制，并确定药物输送的效率。我们还将确定使用叶酸、RGD、半乳糖、转铁蛋白和他莫昔芬靶向的靶向效率。这项为期两年的R21赠款的目标是制定创建纳米级NPSC的策略，并进行细胞培养研究，以证明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，为未来资助期间的动物模型研究提供基础。 公共卫生相关性： 项目叙述：重要性：纳米颗粒稳定的胶囊提供了一种将治疗剂递送到体内特定位置（如肿瘤或器官）的新方法。在我们拟议的研究中，我们将开发新的策略来制造和调整用于递送应用的颗粒，从而为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.