The distribution and retention of paclitaxel and doxorubicin in multicellular layer cultures

  • Authors:
    • Joo-Ho Lee
    • Kun Na
    • Soo-Chang Song
    • Jaehwi Lee
    • Hyo-Jeong Kuh
  • View Affiliations

  • Published online on: January 20, 2012     https://doi.org/10.3892/or.2012.1650
  • Pages: 995-1002
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Abstract

Limited distribution of anticancer drugs has been recognized as a significant hurdle to efficacy. We investigated a detailed penetration/distribution profile of paclitaxel-rhodamine (PTX-rd) and doxorubicin (DOX) in multicellular layer (MCL) cultures of human cancer cells as an in vitro model for avascular regions of solid tumors. MCLs were exposed to drugs and fluorescent images of frozen sections were acquired for determination of drug penetration into MCL under various exposure conditions. PTX-rd and DOX showed drastically different profiles of penetration. DOX showed full penetration after 1 h and accumulation over 3 h, whereas PTX-rd showed slow and limited penetration, with accumulation only within the top 20% of layers by 2 h and insignificant penetration even at 72 h. Drug retention in MCL was more dependent on drug concentration, rather than exposure time, i.e., drug distribution increased by 6.3- and 2.5-fold for PTX-rd and DOX, respectively, when exposed to higher concentrations under comparable AUC exposure (1 µM x 24 h vs. 50 µM x 0.5 h). Anti-proliferative activity of PTX and DOX in MCL, as determined by cell cycle analysis, was minimal and may be attributed, at least in part, to their limited distribution in multicellular cultures. Overall, we demonstrated that penetration and retention of PTX and DOX in MCL was not only concentration- and time-dependent, but also schedule-dependent. It is suggested that slow releasing formulations or a slow infusion regimen may not necessarily be desirable, especially for PTX, due to insufficient penetration and accumulation which may result from a low local concentration at the target site.
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April 2012
Volume 27 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Lee J, Na K, Song S, Lee J and Kuh H: The distribution and retention of paclitaxel and doxorubicin in multicellular layer cultures. Oncol Rep 27: 995-1002, 2012
APA
Lee, J., Na, K., Song, S., Lee, J., & Kuh, H. (2012). The distribution and retention of paclitaxel and doxorubicin in multicellular layer cultures. Oncology Reports, 27, 995-1002. https://doi.org/10.3892/or.2012.1650
MLA
Lee, J., Na, K., Song, S., Lee, J., Kuh, H."The distribution and retention of paclitaxel and doxorubicin in multicellular layer cultures". Oncology Reports 27.4 (2012): 995-1002.
Chicago
Lee, J., Na, K., Song, S., Lee, J., Kuh, H."The distribution and retention of paclitaxel and doxorubicin in multicellular layer cultures". Oncology Reports 27, no. 4 (2012): 995-1002. https://doi.org/10.3892/or.2012.1650