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用于治疗性蛋白质口服递送的过去、现在和未来技术。

Past, present, and future technologies for oral delivery of therapeutic proteins.

作者信息

Singh Rajesh, Singh Shailesh, Lillard James W

机构信息

Department of Microbiology & Immunology, University of Louisville, Louisville, Kentucky 40202, USA.

出版信息

J Pharm Sci. 2008 Jul;97(7):2497-523. doi: 10.1002/jps.21183.

Abstract

Biological drugs are usually complex proteins and cannot be orally delivered due to problems related to degradation in the acidic and protease-rich environment of the gastrointestinal (GI) tract. The high molecular weight of these drugs often results in poor absorption into the periphery when administered orally. The most common route of administration for these therapeutic proteins is injection. Most of these proteins have short serum half-lives and need to be administered frequently or in high doses to be effective. So, difficulties in the administration of protein-based drugs provides the motivation for developing drug delivery systems (DDSs) capable of maintaining therapeutic drug levels without side effects as well as traversing the deleterious mucosal environment. Employing a polymer as an entrapment matrix is a common feature among the different types of systems currently being pursued for protein delivery. Protein release from these matrices can occur through various mechanisms, such as diffusion through or erosion of the polymer matrix, and sometimes a combination of both. Encapsulation of proteins in liposomes has also been a widely investigated technology for protein delivery. All of these systems have merit and our worthy of pursuit.

摘要

生物药物通常是复杂的蛋白质,由于在胃肠道(GI)酸性和富含蛋白酶的环境中会发生降解问题,所以不能口服给药。这些药物的高分子量通常导致口服给药时外周吸收不佳。这些治疗性蛋白质最常见的给药途径是注射。这些蛋白质大多血清半衰期短,需要频繁给药或高剂量给药才能有效。因此,基于蛋白质的药物给药困难促使人们开发能够维持治疗药物水平而无副作用且能穿越有害黏膜环境的药物递送系统(DDS)。使用聚合物作为包封基质是目前正在研究的不同类型蛋白质递送系统的一个共同特点。蛋白质从这些基质中的释放可以通过多种机制发生,例如通过聚合物基质的扩散或侵蚀,有时是两者的结合。将蛋白质包封在脂质体中也是一种广泛研究的蛋白质递送技术。所有这些系统都有优点,值得探索。

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