Fig. 5.

Effect of tumor structure and morphology and drug delivery system on tumor pharmacokinetics. Mice were implanted with IP human xenograft tumors (pancreatic Hs766T, pancreatic MiaPaCa2, or ovarian SKOV3). Omental tumors were excised on 21, 25, and 45 days or about 80% of the median survival time of untreated animals (25, 36, and 52 days, respectively) and stained with hematoxylin and eosin. a Tumor structure and morphology. Top: Whole tumor section (top panels). Note difference in size between the three tumors. Micrographs (×200 magnification) of areas marked in white boxes in the top panel pictures. b Tumor pharmacokinetics. Mice were treated with equi-toxic doses of paclitaxel/Cremophor (40 mg/kg) and TPM (120 mg/kg). Treatments were given when tumors were well established (i.e., 17 and 22 days post-tumor implantation for Hs766T and MiaPaCa2, respectively), and tumors were collected 3 and 7 days post-treatment. The respective tumor weight was 1054 ± 414 mg for Hs766T tumors, and 316 ± 150 mg for MiaPaCa-2 tumors. Note that the results are the sum of total paclitaxel concentration comprising free, protein-bound, cell-associated and particle-associated drug. Horizontal lines are median values. Solid circles and solid lines are for tumors removed 3 days post-treatment. Open circles and dashed horizontal lines are for tumors removed 7 days post-treatment. Data are normalized to 40 mg/kg dose. Note the different y-scales. Reprinted from (4) with permission