In Vivo Fate of End-Chain Radiolabelled Poly(β-malic acid), a Water-Soluble Biodegradable Drug Carrier

Abstract

In a first attempt to determine the fate of poly(β-malic acid) after intravenous injection in mice, polymer end-chain 14 C-radiolabelling was achieved using 14 C-triethylamine as the initiator for the ring-opening polymer ization of benzyl malolactonate. The corresponding poly(β-malic acid) sodium salt ( M w ∼ 30,000) exhibited an activity of 4.2 μCi :g -1 . Aliquots of a neutral isoosmotic solution of the latter were given intravenously to mice through a lateral tail vein. Radioactivity was counted in the liver, kidney, intestine, lung, brain, spleen, heart, muscle, urine and blood for various post-injection times up to 24 hours. Fast urinary excretion (70% after 1 hour and 90% after 6 hours) was observed. For all the sites investigated, radioactivity decreased exponen tially except in the liver and kidneys where a small peak was detected after 2 hours. Further investigations with poly(β-malic acid) radiolabelled in repeat ing units will be necessary to overcome the shortcomings of the end-chain radiolabelling method applied to degradable polymers.