STABILITY CONSIDERATIONS IN DRUG DELIVERY SYSTEMS: PREPARATION, CHARACTERIZATION AND STABILIZATION
D.J.A. Crommelin
Daan Crommelin obtained his pharmacy degree at the University of Groningen in 1975. After a Ph.D. training at the University of Leyden (degree in 1979), he worked as a post-doctoral fellow at the University of Michigan (in 1979/80) with Prof. Dr. W.I. Higuchi. In 1984 he became full professor in Biopharmacy at Utrecht University. At the present time he is Scientific Director of the Utrecht Institute for Pharmaceutical Sciences (UIPS) at Utrecht University in the Netherlands. He is adjunct professor at the School of Pharmacy of Utah, Dept. Pharmaceutics and Pharmaceutical Chemistry (Salt Lake City). He is author and co-author of over 200 original articles in the field of (bio)pharmaceutics and drug targeting, (co)-editor of 6 books. He is member of the editorial board of 10 leading journals in the pharmaceutical sciences. He was associate editor of the Journal of Drug Targeting, special feature editor for Pharmaceutical Research and European Editor of J. Controlled Release. At the present time he is European Editor of Pharmaceutical Research. Between 1989 and 1995 he was scientific secretary of the International Pharmaceutical Federation/Fédération Internationale Pharmaceutique (FIP) and scientific secretary of the FIP Board of Pharmaceutical Sciences. He is Fellow of the American Association of Pharmaceutical Sciences (AAPS). He is scientific director of OctoPlus B.V., a company focused on (new) drug formulation technologies for (bio)pharmaceuticals based in Leyden. His main fields of interest are: advanced drug/gene delivery systems, in particular liposomes and liposome-homing device combinations, drug targeting concepts, characterization and stabilization of proteins and modern vaccines.
Presentation Summary
Protein drugs may need a carrier system to enhance their therapeutic potential. Moreover, sometimes targeted carrier systems bear a homing device that is a protein as well. Examples of this last category are antibody (fragments). For the coupling of these antibodies a number of approaches are presently available that basically bind the protein via an -S-, -SS- , amide or ester bridge to an anchor molecule in the bilayer. Therapeutic proteins can be liposome associated either via embedding in the bilayer, electrostatic interactions with the bilayer, or just by its presence in the aqueous, liposome encapsulated volume fraction. The primary, secondary and tertiary structure of proteins can be disturbed in the preparation stage (presence of e.g., organic solvents, detergents, freezing/thawing, drying, shear forces, interaction with interfaces), during storage (temperature, water content) or during administration (interaction with interfaces, shear). The interaction with a lipid bilayer can (ir)reversibly change the secondary and tertiary structure of protein. But, a protein, while interacting with a bilayer, can also affect the stability of the liposome bilayer. Apart from bioassays, often laborious and providing limited information about the total structure of the protein, modern analytical techniques can help to provide additional information about the features of therapeutic proteins and proteins used as homing devices. Regularly used techniques to monitor proteins in liposomes are circular dichroism spectroscopy, Fourier transform infrared spectroscopy, fluorescence techniques, chromatographic techniques (combined with electrophoresis) and calorimetry. In this presentation examples will be discussed of liposome-protein combinations that are presently under development.