Increased anti-tumor effect of adriamycin-loaded albumin microspheres is associated with anaerobic bioreduction of drug in tumor tissue.

Anti-tumor activity and fate of adriamycin incorporated into biodegradable albumin microspheres was examined in vivo after direct intratumoral injection. Adriamycin in microspherical form displayed superior anti-tumor activity to a comparable dose of drug in solution. This was associated at later time points (40 hr, 50 hr and 72 hr after injection) with higher median parent drug concentrations in tumor tissue (4.1, 3.6, 2.6 micrograms/g respectively for microspheres and 1.6, 1.7 and 1.0 micrograms/g for solution) and the consistent detection of 7-deoxyaglycone metabolites, end products of reduction of adriamycin under anaerobic conditions (1.1, 1.0, 1.0 micrograms/g respectively for microspheres and less than 0.1 micrograms/g at all time points for solution). It is generally considered that the redox properties of anthracyclines are responsible for their toxicity to normal tissues whereas other mechanisms are responsible for antineoplastic activity. In this study we show that inducing metabolism of Adriamycin via reductive pathways is associated with increased anti-tumor effect.