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home > pmps > summer 2003 > controlled release of pharmaceutical proteins from hydrogels
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Pharmaceutical Manufacturing and Packing Sourcer

Controlled Release of Pharmaceutical Proteins from Hydrogels

The therapeutic potential of many pharmaceutical proteins would highly benefit from the availability of controlled release systems for the constant or pulsed release of the intact protein. Several potential candidates for controlled release strategies are listed in Table 1. At present, alternative routes of administration to the parenteral route show little promise except for the pulmonary route.

This article focuses on parenteral delivery systems. So, we 'stick to the needle' but use controlled release delivery systems for these proteins: to produce the desired pharmaco-kinetic profile, for example to prevent high initial plasma concentrations (often 'the flatter, the better'); to reduce the injection frequency and improve patient-friendliness of the therapy; and to reduce the necessity of frequent involvement of trained medical personnel.

A number of strategies have been developed to control the release of proteins as a function of time (1). Proteins have been formulated in amorphous form or as crystals (for example insulin) to ensure release over a short period of up to two days. A second strategy uses a pump with a catheter and fixed needle to administer drugs for local or systemic delivery. These pumps have the advantage of control over pump rate and proven reliability of the technology, but even the miniaturised devices are expensive and become rather bothersome for the patients in the long run. Thirdly, liposomal dispersions release their content over periods of up to three weeks after subcutaneous injection.


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By Ruud Verrijk, Gert Bos and Daan JA Crommelin of OctoPlus Technologies BV, and Wim E Hennink of the Utrecht Institute for Pharmaceutical Sciences, UIPS, Utrecht University

Ruud Verrijk PhD has over 15 years' experience in the pharmaceutical analysis of drugs. He worked as a Postdoc at the Netherlands Cancer Institute, where he was responsible for the formulation and analysis of cytostatics in microspheres, targeting and bioanalysis of cytotoxic precursor drugs. He is author of more than 15 papers on pharmaceutical analysis, drug formulation and pharmacology. He is currently working at OctoPlus Technologies as Manager Research Projects on protein delivery with hydrogels and on non-viral polymeric DNA delivery systems.

Gert Bos PhD obtained his master's in Chemical Technology in 1993 at the University of Twente. He earned his PhD in Biomaterial Science from the same university after which he moved to a business development position at OctoPlus in the Netherlands.

Professor Daan Crommelin PhD is a Professor at the Department of Pharmaceutics at Utrecht University. He is Scientific Director of the Utrecht Institute for Pharmaceutical Sciences (UIPS) and Adjunct Professor at the Department of Pharmaceutics and Pharmaceutical Chemistry at the University of Utah. His research focuses on advanced drug delivery and drug targeting strategies. Professor Crommelin is also Chief Scientific Officer of OctoPlus.

Professor Wim Hennink PhD studied biochemistry at the Agricultural University of Wageningen. He obtained his PhD at the Twente University of Technology on a thesis entitled: Albumin-heparin Conjugate as a Coating for Biomaterials. He previously worked as a Development Engineer within the R&D Department of Fasson in Leiden. In July 1992 he took up his present position and became Head of the Department of Pharmaceutics in 1996. Professor Hennink is European Editor of the J. Controlled Release.
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Ruud Verrijk
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Gert Bos
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Professor Daan Crommelin
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Professor Wim Hennink
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