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Comparison between Microplate Spectrometry and LC/MS Chromato-graphy for Facile Pilot Pharmacokinetics and Biodistribution Studies of Doxorubicin-loaded Nanoparticle Drug Carriers

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Author(s): Pengxiao Cao | Younsoo Bae

Journal: Journal of Applied Pharmaceutical Science
ISSN 2231-3354

Volume: 2;
Issue: 9;
Start page: 001;
Date: 2012;
Original page

Keywords: Drug Delivery | Polymer Micelles | Cross-linked Nanoassemblies | Doxorubicin | Pharmacokinetics | Biodistribution.

ABSTRACT
A facile and reliable method to perform pilot pharmacokinetic (PK) and biodistribution studies is necessary for expediting the overall development and clinical translation of novel nanoparticle drug carriers. In this study, we compared two common analytical techniques, fluorescence spectrometry using a microplate reader and liquid chromatography/mass spectrometry (LC/MS), demonstrating the quantification of a model anticancer drug (doxorubicin: DOX) in its free drug and nanoparticle formulations in vivo. Drug-loadednanoparticle formulations were prepared from poly(ethylene glycol)-poly(aspartate) block copolymers, which formed two model drug carriers with different particle stability, self-assembled polymer micelles(DOX-micelles) and cross-linked nanoassemblies (DOX-CNAs). These three DOX formulations were injected into tumor-bearing mice at a DOX equivalent concentration. DOX levels in liver, spleen, and tumorswere found to be comparable regardless of the analytical methods. LC/MS showed lower serum level than spectrometry with a microplate reader, which is consistent with the fact that DOX metabolites are present mainly in the serum.These results demonstrate that, in comparison to the LC/MS method, spectrometry using a microplate reader would be a viable and more facile method to perform pilot PK and biodistribution studies of various potential nanoparticle drug carriers using DOX as a model drug.
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