Oral drug delivery of proteins is limited by the degradative environment of the gastrointestinal tract and poor absorption, requiring parenteral administration of these drugs. Luminal mucus represents the initial steric and dynamic barrier to absorption. To overcome this barrier, we report the development of the RoboCap, an orally ingestible, robotic drug delivery capsule that locally clears the mucus layer, enhances luminal mixing, and topically deposits the drug payload in the small intestine to enhance drug absorption. RoboCap’s mucus-clearing and churning movements are facilitated by an internal motor and by surface features that interact with small intestinal plicae circulares, villi, and mucus. Vancomycin (1.4 kilodaltons of glycopeptide) and insulin (5.8 kilodaltons of peptide) delivery mediated by RoboCap resulted in enhanced bioavailability 20- to 40-fold greater in ex vivo and in vivo swine models when compared with standard oral delivery ( P < 0.05). Further, insulin delivery via the RoboCap resulted in therapeutic hypoglycemia, supporting its potential to facilitate oral delivery of drugs that are normally precluded by absorption limitations.

中文翻译：

---

RoboCap：用于增强胃肠道药物输送的机器人粘液清除胶囊

蛋白质的口服药物递送受到胃肠道降解环境和吸收差的限制，需要肠胃外施用这些药物。腔内粘液代表吸收的初始空间和动态屏障。为了克服这一障碍，我们报告了 RoboCap 的开发，这是一种口服的机器人药物输送胶囊，可局部清除粘液层，增强管腔混合，并将药物有效负载局部沉积在小肠中以增强药物吸收。RoboCap 的粘液清除和搅拌运动是通过内部电机以及与小肠皱襞、绒毛和粘液相互作用的表面特征来促进的。与标准口服给药相比，由 RoboCap 介导的万古霉素（1.4 千道尔顿糖肽）和胰岛素（5.8 千道尔顿肽）递送在离体和体内猪模型中的生物利用度提高了 20 至 40 倍。磷< 0.05）。此外，通过 RoboCap 输送胰岛素可导致治疗性低血糖，这支持了其促进口服给药的潜力，而这些药物通常因吸收限制而无法口服。