Engineering Particle Nanostructure for Enhanced Bioadhesion

性状（由申请方提供）：口服给药仍然是首选给药途径。然而，目前正在开发的治疗性大分子药物具有较差的口服生物利用度。纳米技术可能提供比传统的药物输送策略的潜在优势。在这个建议中，我们研究纳米纤维的方法来创建纳米线接口，促进动态条件下的生物粘附。我们研究了纳米结构与下层上皮的相互作用，以及使用这种界面来增强药物的局部递送。该提案的长期目标是开发一种新的平台，通过创建一种稳健的生物粘附递送系统，将生物活性大分子口服递送到体循环中。我们提出了以下具体目标：具体目标1：优化工艺，以最佳制造具有可控尺寸、特征几何形状、机械完整性和均匀性的高度均匀的纳米线平台具体目标2：检查细胞-纳米线生物粘附的机制和对体外药物释放的影响具体目标3：使用荧光成像和microCT确定纳米结构颗粒的体内生物粘附性我们期望发现我们的纳米线-与化学改性的颗粒相比，颗粒显示出增强的生物粘附。这可以允许增加颗粒在上皮界面处的停留时间。此外，使用纳米结构来增强颗粒稳定性可以减轻与GI系统中化学修饰的稳定性相关的问题。 公共卫生相关性：口服给药仍然是首选的给药途径，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定位与胃肠道。我们建议使用纳米结构界面来增强递送装置对胃肠道的生物粘附。

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.