Tumor tissue, doxorubicin concentration

Further investigations revealed that the superior antitumor efficacy of Leu-DOX was, indeed, due to site-selective activation and delivery of doxorubicin. At equitoxic intravenous doses of DOX and Leu-DOX (8 and 28 mg/kg, respectively, see above), the plasma levels of DOX attained were comparable, whereas differences were seen in tumor tissue concentrations [51]. The enzymes involved in the tumor-selective activation of Leu-DOX were not identified, although possible candidates include the cathepsin family of proteases [47],... 

Pegylated liposomes (diameter about 70-100 nm) and liposomal daunorubicin (diameter 45 nm) are small enough to pass intact through defective blood vessels that supply tumors. This, rather than any particular affinity for tumor cells, is the reason for their accumulation in tumor tissue (2). Caelyx provides a greater concentration of doxorubicin in Kaposi s sarcoma tumors than in normal skin. 

Indeed, when compared with standard chemotherapy using doxorubicin, the doxorubicin concentrations generated by fusion protein-mediated prodrug activation resulted in 4-12 fold higher doxorubicn concentrations in the tumor and to 2.5 fold lower doxorubicin concentrations in normal tissues (69). 

The significant advance of these beads is the demonstration of an effective process for consistent drug release that controls local tissue response. Recent animal studies on a model of liver cancer have confirmed the in vivo slow release of doxorubicin overtime within the tumor, with maintenance of a high concentration of drug for up to 14 days. Pharmacokinetic data of this study showed near complete absence of doxorubicin within plasma, while intratumoral doxorubicin concentrations remained high [22]. 

Also, according to Arnold et al. [390], the dose scheme of doxorubicin-loaded liposomes affects the drug accumulation in various tissues as well as the tumor. The authors reported that after repetitive doses of sterically stabilized liposomes (SSL)-DOX every week, the plasma half-life of the drug increased, the deposition in liver and spleen decreased, and peak concentrations of DOX in the heart were threefold... 

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