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Physical and Biological Properties of Water Soluble Polyelectrolyte Complexes

Advanced Drug Delivery Research Ciba-Geigy Pharmaceuticals Horsham, West Sussex, U.K.

K.E. Smith

Advanced Drug Delivery Research Ciba-Geigy Pharmaceuticals Horsham, West Sussex, U.K.

L.E.F. Hutchinson

Advanced Drug Delivery Research Ciba-Geigy Pharmaceuticals Horsham, West Sussex, U.K.

J.E. O'Mullane

Advanced Drug Delivery Research Ciba-Geigy Pharmaceuticals Horsham, West Sussex, U.K.

L. Brookman

Advanced Drug Delivery Research Ciba-Geigy Pharmaceuticals Horsham, West Sussex, U.K.

K. Petrak

Advanced Drug Delivery Research Ciba-Geigy Pharmaceuticals Horsham, West Sussex, U.K.

S.E. Harding

Dept. Applied Biochemistry and Food Science University of Nottingham, U.K.

Water soluble non-stoichiometric polyelectrolyte complexes have been investigated as potential drug carrier systems for parenteral administra tion. Complexes between the polycationic quaternized poly(vinyl imidazole) (QPVI) and an excess of a higher molecular weight partially sulfonated dextran (pDS) were designed to inherit the biocompatible properties of dextran. Polyelectrolyte complexes with an overall anionic nature prepared from excess poly(methacrylic acid) (PMAA) and low molecular weight quaternary poly amines were also studied. Sedimentation velocity techniques and size exclu sion chromatography showed that complexation was present in all of the systems studied under the appropriate conditions. These studies also indicated that an increasing [polycation]/[polyanion] ratio resulted in a smaller, more compact complex conformation. Platelet aggregation studies showed that toxic aggregatory effects normally induced by the polycations, and to a lesser extent the pDS, were eliminated in vitro when they formed part of a soluble polyelec trolyte complex. In vivo distribution studies in mice using ¹²⁵I-labelled polyca tion complexed with pDS or PMAA showed accumulation of 40-50% of the ad ministered dose in the liver after 2 hours. The polycation present in these com plexes appears to have been prevented, to some extent, from interacting with negatively-charged biological surfaces, such as platelets in vitro. However this complexation was not sufficient, at least for the macromolecules we have ex amined, to prevent the extensive incidence of unwanted interactions in vivo, lead ing to removal of the polyelectrolyte complexes from the circulation. In conclusion it has been shown that the ionic bonds which hold this type of complex to gether, are not sufliciently strong in vivo to preserve a stable complex structure.

Journal of Bioactive and Compatible Polymers, Vol. 5, No. 3, 267-282 (1990)
DOI: 10.1177/088391159000500303


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