Klepach Alisa, Tran Huyen, Ahmad Mohammed Faiz, ElSayed Mohamed E H
Eli Lilly and Company Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States.
Eli Lilly and Company Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States.
Adv Drug Deliv Rev. 2022 Jul;186:114322. doi: 10.1016/j.addr.2022.114322. Epub 2022 May 6.
Peptides, an emerging modality within the biopharmaceutical industry, are often delivered subcutaneously with evolving prospects on oral delivery. Barrier biology within the subcutis or gastrointestinal tract is a significant challenge in limiting absorption or otherwise disrupting peptide disposition. Aspects of peptide pharmacokinetic performance and ADME can be mitigated with careful molecular design that tailors for properties such as effective size, hydrophobicity, net charge, proteolytic stability, and albumin binding. In this review, we endeavor to highlight effective techniques in qualifying physicochemical properties of peptides and discuss advancements of in vitro models of subcutaneous and oral delivery. Additionally, we will delineate empirical findings around the relationship of these physicochemical properties and in vivo (animal or human) impact. We conclude that robust peptide characterization methods and in vitro techniques with demonstrated correlations to in vivo data are key routines to incorporate in the drug discovery and development to improve the probability of technical and commercial success of peptide therapeutics.
肽作为生物制药行业中一种新兴的药物形式，通常通过皮下注射给药，口服给药的前景也在不断发展。皮下组织或胃肠道内的屏障生物学在限制吸收或以其他方式破坏肽的处置方面是一个重大挑战。通过精心的分子设计，针对有效大小、疏水性、净电荷、蛋白水解稳定性和白蛋白结合等特性进行定制，可以减轻肽的药代动力学性能和药物代谢动力学方面的问题。在本综述中，我们致力于强调鉴定肽物理化学性质的有效技术，并讨论皮下和口服给药体外模型的进展。此外，我们将阐述围绕这些物理化学性质与体内（动物或人类）影响之间关系的实证研究结果。我们得出结论，强大的肽表征方法和与体内数据具有相关性的体外技术是药物发现和开发过程中应纳入的关键常规方法，以提高肽疗法在技术和商业上取得成功的可能性。
