Engineering Particle Nanostructure for Enhanced Bioadhesion

描述(申请人提供)：口服给药仍然是给药的首选途径。然而，目前正在开发的治疗性大分子药物存在口服生物利用度低的问题。与传统的药物输送策略相比，纳米技术可能提供潜在的优势。在这项建议中，我们研究了纳米制造方法，以创建在动态条件下促进生物黏附的纳米线界面。我们研究了纳米结构与底层上皮细胞的相互作用，以及使用这种界面来增强药物的局部输送。这项建议的长期目标是开发一种新的平台，通过创建一个强大的生物黏附递送系统，将药理活性大分子口服递送到全身循环中。我们提出了以下具体目标：具体目标1：优化工艺，以优化制备尺寸、特征几何形状、机械完整性和均一性可控的高度均匀的纳米线平台。具体目标2：研究细胞-纳米线生物黏附的机制及其对体外药物释放的影响。特殊目标3：利用荧光成像和MicroCT确定纳米结构颗粒的体内生物黏附。我们期望发现，与化学修饰的纳米颗粒相比，我们的纳米线颗粒表现出更强的生物黏附。这可能会增加颗粒在上皮界面上的停留时间。此外，使用纳米结构来增强颗粒稳定性可能会缓解与GI系统中化学修饰的稳定性相关的问题。 公共卫生相关性：口服给药仍然是给药的首选途径，特别是在美国。然而，有几个问题与足够的药物生物利用度和胃肠道本地化有关。我们建议使用纳米结构界面来增强递送装置与胃肠道的生物粘附性。

DESCRIPTION (provided by applicant): Oral delivery remains the preferred route for drug administration. However, therapeutic macromolecular drugs currently under development suffer from poor oral bioavailability. Nanotechnology may offer potential advantages over conventional drug delivery stratagems. In this proposal, we investigate nanofabrication approaches to create nanowire interfaces which promote bioadhesion under dynamic conditions. We examine nanostructure interactions with the underlying epithelium and the use of such interfaces to enhance the local delivery of drugs. The long-term objective of this proposal is to develop a new platform for oral delivery of pharmacologically active macromolecules into the systemic circulation via the creation of a robust bioadhesive delivery system. We propose the following specific aims: Specific Aim 1: Refine processes for optimal fabrication of highly uniform nanowire platforms of controllable size, feature geometry, mechanical integrity and uniformity Specific Aim 2: Examine mechanism of cell-nanowire bioadhesion and effects on drug release in vitro Specific Aim 3: Determine the in vivo bioadhesion of nanostructure particles using fluorescent imaging and microCT We expect to find that our nanowire-particles display enhanced bioadhesion compared to chemically modified particles. This may allow for an increase in particle residence time at the epithelial interface. In addition, the use of nanoarchitecture to enhance particle stability may mitigate issues associated with the stability of chemical modification in the GI system. PUBLIC HEALTH RELEVANCE: Oral delivery remains the preferred route for drug administration, particularly in the U.S. However, there are several issues related to adequate drug bioavailability and localization with the GI tract. We propose the use of nanostructure interfaces to enhance the bioadhesion of delivery devices to the GI tract.