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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

Doxorubicin Loaded Dextran-coated Superparamagnetic Iron Oxide Na-noparticles with Sustained Release Property: Intracellular Uptake, Phar-macokinetics and Biodistribution Study

Author(s): Houli Li, Zhiyi Luo, Mingli Peng*, Lili Guo, Fuqiang Li, Weiyi Feng and Yali Cui*

Volume 23, Issue 7, 2022

Published on: 04 June, 2021

Page: [978 - 987] Pages: 10

DOI: 10.2174/1389201022666210604153738

Price: $65

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Abstract

Background: Due to the short biological half-life and serious side effects (especially for heart and kidney), the application of Doxorubicin (Dox) in clinical therapy is strictly limited. To overcome these shortcomings, a novel sustained release formulation of doxorubicin-loaded dextran-coated superparamagnetic iron oxide nanoparticles (Dox-DSPIONs) was prepared.

Objective: The purpose of this study was to evaluate the intracellular uptake behavior of Dox-DSPIONs and to investigate their pharmacokinetics and biodistribution properties.

Method: Confocal laser scanning microscopy was employed to study the intracellular uptake and release properties of Dox from Dox-DSPIONs in SMMC-7721 cells. Simple high-performance liquid chromatography with fluorescence detection (HPLC-FLD) method was established to study the pharmacokinetics and biodistribution properties of Dox-DSPIONs in vivo after intravenous administration and compared with free Dox.

Results: Intracellular uptake experiment indicated that Dox could be released sustainedly from Dox-DSPIONs over time. The pharmacokinetics parameters displayed that the T1/2and AUC0-24h of Dox-DSPIONs were higher than those of free Dox, while the Cmax of Dox-DSPIONs was significantly lower than that of free drug. The biodistribution behaviors of the drug were altered by Dox-DSPIONs in mice, which showed obvious liver targeting, and significantly reduced the distribution of the drug in the heart and kidney.

Conclusion: Dox-DSPIONs have the sustained-release property in vitro and in vivo, which could significantly prolong blood circulation time, improve bioavailability, and reduce the side effects of Dox. Therefore, the novel formulation of the Dox-DSPIONs has the potential as a promising drug delivery system in cancer therapy.

Keywords: Doxorubicin, dextran-coated superparamagnetic iron oxide nanoparticles, sustained release, intracellular uptake, pharmacokinetics, biodistribution, HPLC-FLD

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