Porous Silicon Particles for Oral Drug Delivery

用于口服药物输送的多孔硅颗粒

• 批准号: 6869204
• 负责人: PETER W SWAAN
• 金额: $ 27.08万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6869204
• 关键词: adhesions; atomic force microscopy; biomedical equipment development; blood glucose; cell line; cellular immunity; confocal scanning microscopy; consumable /disposable biomedical equipment; cytotoxicity; drug delivery systems; fluorescent dye /probe; gastrointestinal drug absorption; gastrointestinal epithelium; immune response; laboratory rat; lactate dehydrogenases; lectin; oral administration; particle; pharmacokinetics; polymethacrylate; radiotracer; resin; silicon; streptozotocin; whole body imaging /scanning

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. Microfabrication technology may offer potential advantages over conventional drug delivery stratagems. This technology, combined with appropriate surface chemistry, can permit highly localized delivery of drugs and permeation enhancers. In this proposal, we investigate microfabrication strategies to create reservoir-containing microdevices and a surface chemistry protocol that can be used to bind muco- or cytoadhesives to these platforms. The long-term objective of this proposal is to develop a biomedical microsystem for oral delivery of pharmacologically active macromolecules into the systemic circulation via the creation of a robust hybrid organic/inorganic delivery system. It is expected that the proposed drug delivery system will enable directional release at the lumen-enterocyte interface resulting in elevated local concentrations. The central hypothesis to our proposed research is that the penetration potential of poorly permeable drugs is significantly enhanced by increasing both the epithelial residence time and local concentration. We propose the following specific aims: 1. To asymmetrically conjugate bioadhesive ligands to microdevices 2. To determine the in vitro release mechanism of drug-loaded microsystems 3. To compare the permeation enhancement effects of bioadhesive microdevices against established oral drug delivery standards 4. Test microdevices in vivo for their ability to deliver therapeutically relevant amounts of drug. We expect to find that microdevices can exhibit enhanced biocompatibility and bioadhesion due to our ability to control device architecture in terms of bulk material, shape, size, and surface chemistry. This may allow for the delivery of multiple therapeutic macromolecules in a more controlled and targeted manner to the GI tract.

描述（由申请人提供）： 口服给药仍然是首选的给药途径。然而，目前正在开发的治疗性大分子药物的口服生物利用度较差。微加工技术可能比传统的药物输送策略具有潜在的优势。该技术与适当的表面化学相结合，可以实现药物和渗透促进剂的高度局部递送。在本提案中，我们研究了微加工策略，以创建包含储层的微器件，以及可用于将粘膜或细胞粘附剂结合到这些平台上的表面化学方案。该提案的长期目标是开发一种生物医学微系统，通过创建强大的混合有机/无机输送系统，将药理学活性大分子口服输送到体循环中。预计所提出的药物递送系统将能够在腔-肠细胞界面处定向释放，从而导致局部浓度升高。我们提出的研究的中心假设是，通过增加上皮停留时间和局部浓度，可显着增强渗透性差的药物的渗透潜力。我们提出以下具体目标： 1. 将生物粘附配体不对称地结合到微器件上 2. 确定载药微系统的体外释放机制 3. 比较生物粘附微装置与既定口服给药标准的渗透增强效果 4. 体内测试微型装置输送治疗相关量药物的能力。 我们期望发现，由于我们能够在散装材料、形状、尺寸和表面化学方面控制器件结构，因此微器件可以表现出增强的生物相容性和生物粘附性。这可能允许以更受控和更有针对性的方式将多种治疗大分子递送到胃肠道。