Porous Silicon Particles for Oral Drug Delivery

描述（由申请人提供）： 口服递送仍然是药物施用的优选途径。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。微制造技术可能提供比传统药物递送策略的潜在优势。该技术与适当的表面化学相结合，可以允许药物和渗透增强剂的高度局部化递送。在这项提案中，我们研究了微制造策略，以创建包含mesicir的微器件和表面化学协议，可用于将粘膜或细胞粘附剂结合到这些平台上。该提案的长期目标是开发一种生物医学微系统，通过创建一个强大的混合有机/无机递送系统，将生物活性大分子口服递送到体循环中。预期所提出的药物递送系统将能够在管腔-肠上皮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，渗透性差的药物的渗透潜力显着增强，通过增加上皮停留时间和局部浓度。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型装置上 2.确定载药微系统的体外释放机制 3.比较生物粘附性微装置与已建立的口服药物递送标准的渗透增强效果 4.在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，由于我们能够控制装置结构的散装材料，形状，尺寸和表面化学方面，微型装置可以表现出增强的生物相容性和生物粘附性。这可以允许以更受控和靶向的方式将多种治疗性大分子递送至胃肠道。

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.