School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China.
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Theranostics. 2022 Jan 1;12(3):1419-1439. doi: 10.7150/thno.61747. eCollection 2022.
The past few years has witnessed a booming market of protein and peptide drugs, owing to their superior efficiency and biocompatibility. Parenteral route is the most commonly employed method for protein and peptide drugs administration. However, short plasma half-life protein and peptide drugs requires repetitive injections and results in poor patient compliance. Oral delivery is a promising alternative but hindered by harsh gastrointestinal environment and defensive intestinal epithelial barriers. Therefore, designing suitable oral delivery systems for peptide and protein drugs has been a persistent challenge. This review summarizes the main challenges for oral protein and peptide drugs delivery and highlights the advanced formulation strategies to improve their oral bioavailability. More importantly, major intestinal cell types and available targeting receptors are introduced along with the potential strategies to target these cell types. We also described the multifunctional biomaterials which can be used to prepare oral carrier systems as well as to modulate the mucosal immune response. Understanding the emerging delivery strategies and challenges for protein and peptide drugs will surely inspire the production of promising oral delivery systems that serves therapeutic needs in clinical settings.
在过去的几年中，由于蛋白质和肽类药物具有优越的效率和生物相容性，它们的市场蓬勃发展。肠外途径是给予蛋白质和肽类药物最常用的方法。然而，由于蛋白质和肽类药物的血浆半衰期短，需要重复注射，导致患者顺应性差。口服给药是一种很有前途的替代方法，但受到恶劣的胃肠道环境和防御性肠上皮屏障的阻碍。因此，设计合适的肽和蛋白质药物口服递送系统一直是一个持续的挑战。本文综述了口服蛋白质和肽类药物传递的主要挑战，并强调了提高其口服生物利用度的先进制剂策略。更重要的是，介绍了主要的肠道细胞类型和可用的靶向受体，以及针对这些细胞类型的潜在策略。我们还描述了可用于制备口服载体系统和调节粘膜免疫反应的多功能生物材料。了解蛋白质和肽类药物的新兴传递策略和挑战，必将激发具有治疗潜力的有前途的口服传递系统的产生，以满足临床环境中的治疗需求。
