Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Biogenic Nanotherapeutics Group (BION), Saarbrücken, Germany.
Department of Pharmacy, Saarland University, Saarbrücken, Germany.
Adv Exp Med Biol. 2019;1148:151-172. doi: 10.1007/978-981-13-7709-9_8.
Oral application of therapeutic enzymes is a promising and non-invasive administration that improves patient compliance. However, the gastrointestinal tract poses several challenges to the oral delivery of proteins, including harsh pH conditions and digestive proteases. A promising way to stabilise enzymes during their gastrointestinal route is by modification with polymers that can provide both steric shielding and selective interaction in different digestive compartments. We give an overview of modification technologies for oral enzymes ranging from functionalisation of native proteins, to site-specific mutation and protein-polymer engineering. We specifically focus on enzymes that are active directly in the gastrointestinal lumen and not systemically absorbed. In addition, we discuss examples of microparticle and nanoparticle encapsulated enzymes for improved oral delivery. The modification of orally administered enzymes offers a broad chemical variability and may be a promising tool for enhancing their gastrointestinal stability.
口服应用治疗性酶是一种有前途的非侵入性给药方式，可以提高患者的依从性。然而，胃肠道对蛋白质的口服递送提出了一些挑战，包括苛刻的 pH 条件和消化蛋白酶。通过用聚合物修饰酶来稳定酶在胃肠道中的方法具有广阔的前景，聚合物可以在不同的消化隔室中提供空间位阻和选择性相互作用。我们综述了用于口服酶的修饰技术，范围从天然蛋白质的功能化，到定点突变和蛋白质-聚合物工程。我们特别关注那些在胃肠道腔内直接发挥活性而不被系统吸收的酶。此外，我们还讨论了用于改善口服递送的微粒和纳米颗粒包封酶的实例。口服给予的酶的修饰提供了广泛的化学变异性，可能是增强其胃肠道稳定性的有前途的工具。
