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

Houli Li; Zhiyi Luo; Mingli Peng; Lili Guo; Fuqiang Li; Weiyi Feng; Yali Cui

doi:10.2174/1389201022666210604153738

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

Curr Pharm Biotechnol. 2022;23(7):978-987. doi: 10.2174/1389201022666210604153738.

Authors

Houli Li^{1

2}, Zhiyi Luo^{1

3}, Mingli Peng^{1

4}, Lili Guo¹, Fuqiang Li¹, Weiyi Feng^{5

2}, Yali Cui^{1

3}

Affiliations

¹ National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi\'an, China.
² Department of Pharmacy, The First Affiliated Hospital of Xi\'an Jiaotong University, Xi\'an, China.
³ College of Life Sciences, Northwest University. Xi\'an, China.
⁴ Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University. Xi\'an, China.
⁵ Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an,China.

PMID: 34097591
DOI: 10.2174/1389201022666210604153738

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 AUC_0-24h of Dox-DSPIONs were higher than those of free Dox, while the C_max 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; HPLC-FLD; biodistribution; dextran-coated superparamagnetic iron oxide nanoparticles; intracellular uptake; pharmacokinetics; sustained release.

MeSH terms

Animals
Delayed-Action Preparations
Dextrans
Doxorubicin / pharmacology
Drug Carriers / chemistry
Drug Delivery Systems
Magnetite Nanoparticles* / chemistry
Mice
Nanoparticles* / chemistry
Tissue Distribution

Substances

Delayed-Action Preparations
Dextrans
Drug Carriers
Magnetite Nanoparticles
Doxorubicin
ferumoxides

Abstract

MeSH terms

Substances

Grants and funding