Effects of core size and PEG coating layer of iron oxide nanoparticles on the distribution and metabolism in mice

Abstract

Weiming Xue,1 Yanyan Liu,1 Na Zhang,1 Youdong Yao,2 Pei Ma,1 Huiyun Wen,1 Saipeng Huang,1 Yane Luo,3 Haiming Fan4 1School of Chemical Engineering, Northwest University, Xi’an, Shaanxi 710069, China; 2Pediatrics, Egang Hospital, Ezhou, Hubei 436000, China; 3College of Food Science and Technology, Northwest University, Xi’an, Shaanxi 710069, China; 4Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an, Shaanxi 710069, China Introduction: In vivo distribution of polyethylene glycol (PEG)ylated functional nanoparticles is vital for determining their imaging function and therapeutic efficacy in nanomedicine. However, contradictory results have been reported regarding the effect of core size and PEG surface of the nanoparticles on biodistribution.Methods: To clarify this ambiguous understanding, using iron oxide nanoparticles (IONPs) as a model system, we investigated the effect of core size and PEG molecule weights on in vivo distribution in mice. Three PEGylated IONPs, including 14 nm IONP@PEG2,000, 14 nm IONP@PEG5,000, and 22 nm IONP@PEG5,000, were prepared with a hydrodynamic size of 26, 34, and 81 nm, respectively. The blood pharmacokinetics and tissue distribution were investigated in detail.Results: The results indicated that the PEG layer, rather than core size, played a dominant role in determining the half-life time of IONPs. Specifically, increased molecular weight of the PEG layer led to a longer half-life time. These PEGylated IONPs were mainly excreted by liver clearance. While the PEG molecular layer constituted the key factor to determine the clearance ratio, core size affected the clearance rate.Conclusion: Complete blood count analysis and histopathology suggested excellent biocompatibility of PEGylated IONPs for future clinical trials. Keywords: IONPs, pharmacokinetics, tissue distribution, metabolism, histocompatibility

Keywords

• IONPs
• pharmacokinetics
• tissue distribution
• metabolism
• histocompatibility.