Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 7, Issue 4, Pages 435-444Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2010.12.009
Keywords
Pharmacokinetics; Multidrug-resistant cancer; Nanoparticles; Lonidamine; Paclitaxel
Funding
- National Cancer Institute, National Institutes of Health [R01 CA-119617, R01 CA-119617S1, R21 CA-135594]
Ask authors/readers for more resources
The aim of this study was to assess the biodistribution and pharmacokinetics of epidermal growth factor receptor (EGFR)-targeted polymer-blend nanoparticles loaded with the anticancer drugs lonidamine and paclitaxel. Plasma, tumor, and tissue distribution profiles were quantified in an orthotopic animal model of multidrug-resistant breast cancer and were compared to treatment with nontargeted nanoparticles and to treatment with drug solution. A poly(d, l-lactide-co-glycolide)-poly(ethylene glycol)-EGFR targeting peptide (PLGA-PEG-EFGR peptide) construct was synthesized for incorporation in poly(epsilon-caprolactone) particles to achieve active EGFR targeting. An isocratic high-pressure liquid chromatography method was developed to quantify lonidamine and paclitaxel in mice plasma, tumors, and vital organs. The targeted nanoparticles demonstrated a superior pharmacokinetic profile relative to drug solution and nontargeted nanoparticles, particularly for lonidamine delivery. The first target site of accumulation was the liver, followed by the kidneys, and then the tumor mass; maximal tumor accumulation occured at 3 hours after administration. Lonidamine-paclitaxel combination therapy administered via EGFR-targeted polymer-blend nanocarriers may become a viable platform for the future treatment of multidrug-resistant cancer. From the Clinical Editor: In this study the biodistribution and pharmacokinetics of epidermal growth factor receptor (EGFR)-targeted polymer-blend nanoparticles loaded with lonidamine and paclitaxel were assessed. The targeted nanoparticles demonstrated a superior pharmacokinetic profile relative to drug solution and nontargeted nanoparticles, paving the way to new therapeutic approaches for multidrug-resistant malignancies. (C) 2011 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available