Tran Huyen, ElSayed Mohamed E H
Senior Advisor, Eli Lilly and Company Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, USA.
Senior Research Fellow, Eli Lilly and Company Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana.
Expert Opin Drug Deliv. 2022 Feb;19(2):163-178. doi: 10.1080/17425247.2022.2051476. Epub 2022 Mar 14.
Numerous formulation technologies have been developed to overcome challenges of oral peptide delivery. Understanding the advantages and limitations of each technology is important for the development of new delivery systems to enable oral delivery of peptides designed for parenteral administration.
This review summarizes key learnings from the use of permeation enhancers (PEs) for oral peptide delivery associated with solid dosage form optimization to maximize the PE effect. Furthermore, we will highlight the most recent emerging delivery strategies to improve oral peptide bioavailability such as nanoparticles, self-emulsifying drug delivery systems, gut shuttles, and ingestible devices. In addition, advantages and limitations of these technologies will be compared with the permeation enhancer technology.
Despite the success of permeation enhancer technology in the FDA-approved oral peptide products, oral peptide delivery is still facing the immense challenge of low-to-single digit oral bioavailability. Optimization of drug product attributes such as dissolution kinetics is critical to improve permeation enhancer efficacy. The next frontiers to substantially increase oral bioavailability and transform injectable peptides to oral deliverables may be ingestible devices and ligand-mediated transport (gut shuttles). However, clinical studies are necessary to inform the safety and efficacy of these emerging technologies.
为克服口服肽递送的挑战，已开发出多种制剂技术。了解每种技术的优势和局限性对于开发新的递送系统至关重要，这些新系统能够实现为肠胃外给药设计的肽的口服递送。
本综述总结了使用渗透促进剂（PEs）进行口服肽递送并结合固体剂型优化以最大化PE效果的关键经验教训。此外，我们将重点介绍提高口服肽生物利用度的最新新兴递送策略，如纳米颗粒、自乳化药物递送系统、肠道穿梭载体和可摄入装置。此外，将把这些技术的优势和局限性与渗透促进剂技术进行比较。
尽管渗透促进剂技术在FDA批准的口服肽产品中取得了成功，但口服肽递送仍面临着低至个位数口服生物利用度这一巨大挑战。优化药物产品属性（如溶解动力学）对于提高渗透促进剂的疗效至关重要。大幅提高口服生物利用度并将注射用肽转变为口服制剂的下一个前沿领域可能是可摄入装置和配体介导的转运（肠道穿梭载体）。然而，需要进行临床研究以了解这些新兴技术的安全性和有效性。
