Journal
JOURNAL OF CONTROLLED RELEASE
Volume 278, Issue -, Pages 66-73Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2018.03.024
Keywords
In vivo flow cytometry; Nanoparticle clearance; Nanoparticle aggregation; Noninvasive imaging; Blood circulation
Funding
- National Science Fund for Distinguished Young Scholars [61425006]
- National Nature Science Foundation of China [61227017, 81573382]
- Shu Guang project - Shanghai Municipal Education Commission [15SG14]
- Shanghai Education Development Foundation
- National Major Scientific Research Program of China [2011CB910404, 2012CB966801]
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Nanoparticles have been widely used in biomedical research as drug carriers or imaging agents for living animals. Blood circulation is crucial for the delivery of nanoparticles, which enter the bloodstream through injection, inhalation, or dermal exposure. However, the clearance kinetics of nanoparticles in blood circulation has been poorly studied, mainly because of the limitations of conventional detection methods, such as insufficient blood sample volumes or low spatial-temporal resolution. In addition, formation of nanoparticle aggregates is a key determinant for biocompatibility and drug delivery efficiency. Aggregation behavior of nanoparticles in blood is studied using dynamic light scattering in serum or serum protein solutions, which is still very different from in vivo condition. In this work, we monitored the dynamics of nanoparticle concentration and formation of nanoparticle aggregates in the bloodstream in live animals using in vivo flow cytometry (IVFC). The results indicated that nanoparticles in smaller size could stay longer in the bloodstream. Polyethylene glycol (PEG)-modification could prolong circulating time and reduce the formation of aggregates in the blood circulation. Our work shows that IVFC can be a powerful tool for pharmacokinetic studies of nanoparticles and other drug carriers, assessing cell-targeting efficiency, as well as potentially measuring cardiac output and hepatic function in vivo.
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