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Journal of Bioactive and Compatible Polymers
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Soluble Polymeric Carriers for Drug Delivery - Part 6: Preparation and Biodistribution of N5-Hydroxyethyl-L-Glutamine-co-L-Glutamic Acid Copolymers in Rats

Deborah Bayley

Department of Drug Preformulation and Delivery CIBA-GEIGY Pharmaceuticals Wimblehurst Road, Horsham, West Sussex, RH12 4AB United Kingdom

Marie-Rose Sancho

Department of Drug Preformulation and Delivery CIBA-GEIGY Pharmaceuticals Wimblehurst Road, Horsham, West Sussex, RH12 4AB United Kingdom

Janet Brown

Department of Drug Preformulation and Delivery CIBA-GEIGY Pharmaceuticals Wimblehurst Road, Horsham, West Sussex, RH12 4AB United Kingdom

Laurence Brookman

Department of Drug Preformulation and Delivery CIBA-GEIGY Pharmaceuticals Wimblehurst Road, Horsham, West Sussex, RH12 4AB United Kingdom

Karel Petrak

Department of Drug Preformulation and Delivery CIBA-GEIGY Pharmaceuticals Wimblehurst Road, Horsham, West Sussex, RH12 4AB United Kingdom

Peter Goddard

Department of Drug Preformulation and Delivery CIBA-GEIGY Pharmaceuticals Wimblehurst Road, Horsham, West Sussex, RH12 4AB United Kingdom

Alan Steward

Department of Drug Preformulation and Delivery CIBA-GEIGY Pharmaceuticals Wimblehurst Road, Horsham, West Sussex, RH12 4AB United Kingdom

The purpose of this work was to examine the biodistribution of poly( N5-hydroxyethyl-L-glutamine-co-L-glutamic acid) [poly(HEG- co-GA)] after intravenous administration to rats. Poly({gamma}-methyl-L-glutamate- co-{gamma}-benzyl-L- glutamate) was prepared by ring-opening polymerization of the amino acid N-carboxyanhydride (NCA) derivatives. Sequential removal of the copolymer benzyl groups followed by reaction of the methyl ester groups with 2-amino ethanol gave poly(HEG-co-GA). Three samples of poly(HEG-co-GA) were pre pared with nominal HEG:GA compositions of 50:50, 95:5 and 90:10 mole %, and with weight average molecular weights ( Mw) of 37,000, 50,000 and 110,000 respectively. Following reaction with N-2[4-hydroxyphenyl]ethylamine (tyra mine), the copolymers were radioiodinated with 125 I and administered intra venously to male Wistar rats. 125 I-copolymer tissue distribution was assessed after 10, 15, 30 and 120 min and 8 h. It was found that the copolymer was removed rapidly from the blood compartment and excreted from the body via the kidneys. Only very low amounts of radioactivity were found in the liver and in other organs of the mononuclear phagocyte system. Degradation of the co polymer in vitro, as assessed by size exclusion chromatography (SEC), in plasma and urine over the time scale of the biodistribution experiment ap peared to be minimal.

Journal of Bioactive and Compatible Polymers, Vol. 8, No. 1, 51-68 (1993)
DOI: 10.1177/088391159300800104
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