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In vivo Fate of Repeat-Unit-Radiolabelled Poly(ß-malic acid), a Potential Drug Carrier

Groupe de Pharmacocinétique des Conjugués Macromoléculaires Laboratoire de Technologie Enzymatique U.R.A. n° 1442 du CNRS-Université de Compiègne BP 649, 60206 Compiègne Cedex, France

Dominique Domurado

Groupe de Pharmacocinétique des Conjugués Macromoléculaires Laboratoire de Technologie Enzymatique U.R.A. n° 1442 du CNRS-Université de Compiègne BP 649, 60206 Compiègne Cedex, France

Philippe Guerin

Laboratoire de Chimie Biologique et Macromoléculaire ENSC de Rennes 35700 Rennes-Beaulieu, France

Christian Braud

, U.R.A. n° 500 du CNRS- Université de Rouen Laboratoire des Substances Macromoléculaires INSA de Rouen BP 8, 76131 Mont Saint Aigan Cedex, France

Michel Vert

, U.R.A. n° 500 du CNRS- Université de Rouen Laboratoire des Substances Macromoléculaires INSA de Rouen BP 8, 76131 Mont Saint Aigan Cedex, France

Renee Pontikis

Laboratoire de Chimie et Biochimie Pharmacologique et Toxicologique U.R.A. n° 400 du CNRS-Université René Descartes 45, Rue des Saints Pères 75270 Paris Cedex, France

In order to compare the fates of end-chain-radiolabelled and repeat-unit-radiolabelled poly(ß-malic acid)s after intravenous injection in mice, repeat-unit ¹⁴C-radiolabelling of this biodegradable water-soluble poly carboxylic acid polymer was achieved starting from ¹⁴C-aspartic acid. The ac tivity of the resulting radioactive poly(ß-malic acid) (sodium salt) (Mw 20,000 as determined by aqueous SEC) was 4.5 µCi·g ^-1. Aliquots of a neutral 0.3 monoM (4.14% w/v) solution of poly(ß-malic acid) (sodium salt) were given intravenously to mice through a lateral tail vein. Intravenous and intra peritoneal toxicity was checked in order to show whether injection of this polymer can affect significantly the normal behavior of experimental animals. Radioactivity was counted in liver, kidney, intestine, lung, brain, spleen, heart, muscle, urine and blood for various post-injection times up to 24 h. Data con firmed the occurrence of predominant and fast urinary excretion (70% after 1 h) already observed with the end-chain-radiolabelled homologue. Although the polymer is basically metabolizable, the fast elimination of radioactivity via urinary tract is most likely to be due to the excretion of polymeric molecules and not of metabolic by-products because end-chain- and repeat-unit-labellings led to similar excretion patterns.

Key Words: radiolabelling • biodegradable • poly(ß-malic acid) • elimination • pharmacokinetics • drug carrier • radioactivity • 14C-labelled • toxicity.

Journal of Bioactive and Compatible Polymers, Vol. 7, No. 2, 113-129 (1992)
DOI: 10.1177/088391159200700201


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