کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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877811 | 911048 | 2011 | 10 صفحه PDF | دانلود رایگان |
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(ɛ-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 EditorIn 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.
Graphical AbstractNear-IR fluorescence imaging of control (non-targeted) and epidermal growth factor receptor (EGFR)-targeted polymeric nanoparticles in nude mice with human, multi-drug resistance, breast tumor xenografts. X-ray and fluorescence images were acquired from 15 minutes until 6 hours post-administration of DiR-encapsulated nanoparticles through the tail vein.Figure optionsDownload high-quality image (45 K)Download as PowerPoint slide
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 7, Issue 4, August 2011, Pages 435–444