Institute for Chemical and Bioengineering, ETH, Wolfgang-Pauli-Str. 10, 8093 Zurich, Switzerland.
Institute for Chemical and Bioengineering, ETH, Wolfgang-Pauli-Str. 10, 8093 Zurich, Switzerland.
J Control Release. 2014 Apr 28;180:134-49. doi: 10.1016/j.jconrel.2014.02.002. Epub 2014 Feb 14.
PEGylation is a versatile drug delivery technique that presents a particularly wide range of conjugation chemistry and polymer structure. The conjugated protein can be tuned to specifically meet the needs of the desired application. In the area of drug delivery this typically means to increase the persistency in the human body without affecting the activity profile of the original protein. On the other hand, because of the high costs associated with the production of therapeutic proteins, subsequent operations imposed by PEGylation must be optimized to minimize the costs inherent to the additional steps. The closest attention has to be given to the PEGylation reaction engineering and to the subsequent purification processes. This review article focuses on these two aspects and critically reviews the current state of the art with a clear focus on the development of industrial scale processes which can meet the market requirements in terms of quality and costs. The possibility of using continuous processes, with integration between the reaction and the separation steps is also illustrated.
聚乙二醇化是一种多功能的药物传递技术，提供了特别广泛的缀合化学和聚合物结构。缀合蛋白可以进行调整，以专门满足所需应用的需求。在药物传递领域，这通常意味着增加在人体中的持久性，而不影响原始蛋白的活性谱。另一方面，由于治疗性蛋白的生产相关成本较高，聚乙二醇化后的后续操作必须进行优化，以最小化额外步骤所固有的成本。最密切关注的是聚乙二醇化反应工程和随后的纯化过程。本文重点关注这两个方面，并批判性地回顾了当前的最新技术状态，明确关注能够满足质量和成本方面市场需求的工业规模工艺的发展。还说明了使用连续工艺的可能性，以及反应和分离步骤之间的集成。
