title: Tumor accumulation of liposomal doxorubicin in three murine models: Optimizing delivery efficiency.
abstract: 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.
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD.
authors.forename: Charlene M
authors.initials: CM
authors.lastname: Dawidczyk
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD.
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Russell
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD.
authors.forename: Margot
authors.initials: M
authors.lastname: Hultz
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: searson@jhu.edu.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Searson
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D008081:Liposomes / Q000627:therapeutic use; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Extravasation; Liposomes; Pharmacokinetics; Tumor accumulation