Abstract：
In this contribution to the Orations - New Horizons of the Journal of Controlled Release, I discuss the research that we have conducted on gut hormone stimulation as a therapeutic strategy in oral peptide delivery. One of the greatest challenges in oral drug delivery involves the development of new drug delivery systems that enable the absorption of therapeutic peptides into the systemic circulation at therapeutically relevant concentrations. This scenario is especially challenging in the treatment of chronic diseases (such as type 2 diabetes mellitus), wherein daily injections are often needed. However, for certain peptides, there may be an alternative in drug delivery to meet the need for increased peptide bioavailability; this is the case for gut hormone mimetics (including glucagon-like peptide (GLP)-1 or GLP-2). One plausible alternative for improved oral delivery of these peptides is the co-stimulation of the endogenous secretion of the hormone to reach therapeutic levels of the peptide. This oration will be focused on studies conducted on the stimulation of gut hormones secreted from enteroendocrine L cells in the treatment of gastrointestinal disorders, including a critical discussion of the limitations and future perspectives of implementing this approach in the clinical setting.
摘要：
在对《受控释放杂志》的《Orations-新视野》的贡献中，我讨论了我们对肠道激素刺激作为口服肽递送治疗策略进行的研究。口服药物递送的最大挑战之一涉及开发新的药物递送系统,其能够以治疗相关浓度将治疗性肽吸收到体循环中。这种情况在慢性疾病（如2型糖尿病）的治疗中尤其具有挑战性，其中经常需要每天注射。然而,对于某些肽，在药物递送方面可能存在替代方案以满足增加肽生物利用度的需要;对于肠道激素模拟物(包括胰高血糖素样肽(GLP)-1或GLP-2)就是这种情况.改善这些肽的口服递送的一个可能的替代方案是共刺激激素的内源性分泌以达到肽的治疗水平。本文将集中于对胃肠疾病治疗中从肠内分泌L细胞分泌的肠激素的刺激进行的研究。包括对在临床环境中实施这种方法的局限性和未来观点的批判性讨论。
