John Bresland

A simple and inexpensive enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine *

Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose 13C sodium acetate (13C-acetate), which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of 13CO2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT® L100-55 on gelatin capsules and also on DRcaps®. Test results demonstrated that DRcaps® coated with EUDRAGIT® L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.總結目 的通过开展胃肠道远端释放药物的研究,以增加对肠道健康和发病机制的理解。创新点本研究选择了13C 醋酸钠作为同位素探针,通过收集和分析呼吸中的13CO2 来非侵入测量其在小肠吸收的情况。这将提供胃排空率的信息及释放和吸收位点的指标。方 法在一系列体外和体内的猪实验中,评估了 EUDRAGIT® L100-55 和DRcaps®两种胶囊的肠溶保护特性。结 论包覆有EUDRAGIT® L100-55 的DRcaps®具有增强的肠溶保护性能,特别是在体内。本研究增加了对猪胃排空的了解,同时也开始设计用于递送酸度敏感大分子到小肠的简易且廉价的肠溶胶囊。