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

Abstract

In order to compare the fates of end-chain-radiolabelled and repeat-unit-radiolabelled poly(β-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(β-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(β-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.

Keywords

radiolabelling biodegradable poly(β-malic acid)elimination pharmacokinetics drug carrier radioactivity 14C-labelled toxicity.

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