The plasma and tissue distribution of
doxorubicin-poly-
L-aspartic acid (
DX-PAA) and
doxorubicin (DX) at equitoxic doses have been studied by a fluorescence assay in
tumor bearing mice following administration of a single i.v. bolus injection. A relatively short distribution phase followed by a slow elimination phase characterized the
DX-PAA plasma disappearence: at 48 hr after the treatment the conjugate was still detected in plasma. The plasma under the concentration vs. time curve (AUC) of
drug equivalents following free DX administration resulted 2.6 times higher than the plasma AUC of free equivalents produced by
DX-PAA treatment. In lung, liver and spleen the
DX-PAA was accumulated in high concentrations. Low amount of DX equivalents were found in the heart following the conjugate administration: after 2 hr only traces of free
anthracycline equivalents were detectable. On the contrary,
drug equivalents following free DX treatment remained evaluable in the heart up to 24 hr from the
drug administration. No significative differences were observed in the
tumor AUC of free DX equivalents produced by free or
polymer-linked DX. These data suggest that
DX-PAA might act as a depot system slowly releasing the
cytotoxic agent. Furthermore the observed accumulation of the conjugate and free DX equivalents in the lung and in the liver suggest a possible therapeutic advantages of
DX-PAA in
tumors with potential
metastasis in these organs.