In vivo fates of degradable poly(ß-malic acid)and of its precursor, malic acid

To determine whether degradation could influence the in vivo elimination pattern of poly(ß-malic acid)in mice, radioactive urinary excretion and 14CO2 expiration were studied after intravenous injection of 14C-radiolabeled poly(ß-malic acid)and of its precursor, 14C-malate. The precursor administration led to rapid 14CO2 exhalation, and only negligible urinary elimination. The reverse was observed for the polymer. It was concluded that: (i)the in vivo degradation of poly(ß-malic acid)chains, if any during the 24-h period of the study, did not release detectable malate molecules, (ii)the large urinary excretion of poly(ß-malic acid)was due to the molar masses being less than the renal filtration threshold, (iii)the degradation of the poly(ß-malic acid)chains in blood was slow enough to allow the fraction with higher molar masses to enter the interstitial space of the tissues, and possibly cells.