Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA.
Adv Drug Deliv Rev. 2013 Jun 15;65(6):811-21. doi: 10.1016/j.addr.2013.04.006. Epub 2013 Apr 20.
Successful administration of therapeutic proteins via the oral route has long eluded the drug delivery community; a variety of factors, both physical and physiological, have hindered the myriad approaches to increasing the bioavailability of orally administered therapeutic proteins, including: 1) pre-systemic degradation by enzymes and 2) poor penetration of the intestinal mucosa and epithelium. Even when bypassing the harsh, acidic environment of the stomach, the intestines pose significant obstacles to systemic uptake. For example, the lining of the gastrointestinal tract comprises a thick wall of epithelial cells covered by a layer of polysaccharides and mucus. In this review, we will discuss the biology underlying intestinal uptake of protein-containing, biodegradable nanoparticles, review insulin delivery as the most accepted model for oral delivery of proteins, and present a variety of new material systems enabling novel approaches to oral protein delivery which we believe will bring to bear the next therapeutic advances in our field.
经口服途径给予治疗性蛋白的方法一直以来都令药物输送领域的研究人员感到困扰；多种物理和生理因素阻碍了增加口服给予的治疗性蛋白生物利用度的各种方法，包括：1）酶的全身性前降解和 2）肠黏膜和上皮的通透性差。即使绕过胃的恶劣酸性环境，肠道也对全身吸收构成重大障碍。例如，胃肠道的衬里由一层厚厚的上皮细胞组成，这些细胞被一层多糖和黏液覆盖。在这篇综述中，我们将讨论肠道摄取含蛋白质的可生物降解纳米颗粒的生物学基础，回顾胰岛素输送作为蛋白质口服递送的最被接受的模型，并介绍各种新的材料系统，这些系统使口服蛋白递送的新方法成为可能，我们相信这将为我们领域的治疗进展带来新的突破。
