Table 1.

Plasma pharmacokinetics of free, liposomal, and anti-EGFR immunoliposomal doxorubicin in adult rats

Treatment*t1/2 (h)AUC (μg h/mL)CL (mL/h)Vd (mL)MRT (h)DOX-to-PL (%ID/%ID)
Ls-DOX21.5 ± 2.02,025 ± 1702.48 ± 0.2176.5 ± 0.731.0 ± 2.889.14 ± 0.39
Anti-EGFR ILs-DOX20.7 ± 3.31,836 ± 1652.74 ± 0.2581.1 ± 5.929.9 ± 4.984.67 ± 1.92
  • Abbreviations: AUC, area under the plasma concentration versus time curve based on the sum of exponential terms; MRT, mean residence time calculated from exponential terms; CL, clearance calculated from exponential terms; Vd, volume of distribution.

  • * Liposomal doxorubicin (Ls-DOX) and anti-EGFR immunoliposome-doxorubicin (Anti-EGFR ILs-DOX) were prepared using DSPC/Chol/PEG-DSPE (3:2:0.3, mol/mol/mol) and loaded with doxorubicin at a ratio of 150 g doxorubicin/mol phospholipid using the ammonium sulfate gradient-loading method as described in Materials and Methods. Anti-EGFR immunoliposome-doxorubicin or nontargeted liposomes were administered i.v. at a single dose of 5 mg doxorubicin/kg; two animals per group.

  • Ratio of doxorubicin-to-phospholipid at the 48-hour time point.