Università degli Studi di Milano, Dipartimento di Scienze Farmaceutiche "P. Pratesi", Milan, Italy.
Adv Drug Deliv Rev. 2012 May 1;64(6):540-56. doi: 10.1016/j.addr.2011.10.006. Epub 2011 Nov 6.
Oral colon delivery is currently considered of importance not only for the treatment of local pathologies, such as primarily inflammatory bowel disease (IBD), but also as a means of accomplishing systemic therapeutic goals. Although the large bowel fails to be ideally suited for absorption processes, it may indeed offer a number of advantages over the small intestine, including a long transit time, lower levels of peptidases and higher responsiveness to permeation enhancers. Accordingly, it has been under extensive investigation as a possible strategy to improve the oral bioavailability of peptide and protein drugs. Because of a strong underlying rationale, most of these studies have focused on insulin. In the present review, the impact of key anatomical and physiological characteristics of the colon on its viability as a protein release site is discussed. Moreover, the main formulation approaches to oral colon targeting are outlined along with the design features and performance of insulin-based devices.
口服结肠递药系统目前不仅被认为对局部疾病(如主要的炎症性肠病[IBD])的治疗很重要,而且也是实现全身治疗目标的一种手段。尽管大肠并不完全适合吸收过程,但它确实比小肠具有许多优势,包括较长的转运时间、较低水平的肽酶和对渗透促进剂的更高反应性。因此,它作为一种提高肽类和蛋白质类药物口服生物利用度的策略受到了广泛的研究。由于有坚实的理论基础,这些研究大多集中在胰岛素上。在本文综述中,讨论了大肠的关键解剖和生理特征对其作为蛋白质释放部位的可行性的影响。此外,还概述了口服结肠靶向的主要制剂方法以及基于胰岛素的制剂的设计特点和性能。