INVIVO FATE OF REPEAT-UNIT-RADIOLABELED POLY(BETA-MALIC ACID), A POTENTIAL-DRUG CARRIER

In order to compare the fates of end-chain-radiolabelled and repeat-unit-radiolabelled poly(beta-malic acid)s after intravenous injection in mice, repeat-unit C-14-radiolabelling of this biodegradable water-soluble poly-carboxylic acid polymer was achieved starting from C-14-aspartic acid. The activity of the resulting radioactive poly(beta-malic acid) (sodium salt) (Mw approximately 20,000 as determined by aqueous SEC) was 4.5-mu-Ci.g-1. Aliquots of a neutral 0.3 monoM (4.14% w/v) solution of poly(beta-malic acid) (sodium salt) were given intravenously to mice through a lateral tail vein. Intravenous and intraperitoneal 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 confirmed 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.