Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 13, Issue 5, Pages 1637-1644Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2017.02.008
Keywords
Liposomes; Tumor accumulation; Extravasation; Pharmacokinetics
Funding
- National Institutes of Health [U54CA151838]
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Systemic drug delivery to a solid tumor involves a sequence of steps that determine efficacy and survival. Extravasation from circulation at the tumor site is a critical step in this sequence since it regulates how much of the drug accumulates in the tumor. Despite its importance in determining outcomes, extravasation from circulation remains a black box. The objective of this study is to develop predictive tools for optimization of drug delivery systems. By comparing pharmacokinetics of liposomal doxorubicin in tumor-free and tumor bearing mice we quantitatively assess the rate constants for distribution, elimination, and tumor accumulation. We then relate these rate constants to the tumor-type and drug delivery system. We compare tumor accumulation in three tumor types and show a 10-fold difference between a colorectal adenocarcinoma and a pancreatic adenocarcinoma. Finally, we show how quantitative predictions of changes in tumor accumulation can be used to optimize drug delivery systems. (C) 2017 Elsevier Inc. All rights reserved.
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