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PASylation as a Powerful Technology for Improving the Pharmacokinetic Properties of Biopharmaceuticals

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Bckground: One of the major challenges of biopharmaceuticals having short plasma half-life is that daily high dose injections are needed which can lead to economic burden, patient inconvenience and undesirable side effects. Increasing the hydrodynamic volume beyond the pore size of the glomerular basal membrane is a viable approach to increase the size of small biopharmaceuticals with short half-life in blood circulation.

Objectives: PASylation technology is based on the genetic fusion of biopharmaceuticals with a hydrophilic random coil sequence of proline (Pro), alanine (Ala), and serine (Ser) amino acids.

Method: In this review, we focus on PASylation technology as a novel method to enhance the pharmacokinetic (PK) properties of biopharmaceuticals.

Results: PASylated biopharmaceuticals are suitable for the production in Escherichia coli (E.coli) as well as eukaryotic expression systems like yeast, HEK or CHO cells and comprise a homogeneous PAS sequence with exact length.We explain the general concept of PASylation, its development; advantages compared to other PK modifying technologies and describe furthermore the pharmacodynamic (PD) and PK properties of several PAS-fusion proteins in preclinical studies.

Conclusion: The biodegradable PAS sequence was already used for prolonging plasma half-life of clinical important agents such as antibody fragments, cytokines, enzymes and receptor-binding peptides.
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Keywords: ESETEC technology; PASylation; biodistribution; biopharmaceutical; radiopharmaceutical; tumor targeting

Document Type: Review Article

Publication date: March 1, 2018

This article was made available online on December 8, 2017 as a Fast Track article with title: "PASylation as a Powerful Technology for Improving the Pharmacokinetic Properties of Biopharmaceuticals".

More about this publication?
  • The aim of Current Drug Delivery is to publish peer-reviewed articles, short communications, short and in-depth reviews in the rapidly developing field of drug delivery. Modern drug research aims to build in delivery properties of a drug at the design phase, however in many cases this ideal cannot be met and the development of delivery systems becomes as important as the development as the drugs themselves.

    The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.

    The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.
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