Effect of particle size on the pharmacokinetics and biodistribution of parenteral nanoemulsions

Highlights

• • Labeling by ACQ fluorophores enabled accurate bioimaging of nanoemulsions.
  • Nanoemulsions were cleared rapidly from the blood.
  • Nanoemulsions were mainly taken up by the liver after intravenous administration.
  • Particle size has significant influence on the pharmacokinetics and biodistribution of nanoemulsions.

This study aims to investigate the effect of particle size on the pharmacokinetics and biodistributions of parenteral blank nanoemulsions (NEs). To monitor intact NEs in vivo, a near-infrared fluorescent dye is utilized to label NEs by exploiting its aggregation-caused quenching (ACQ) properties. After a single intravenous dose of NEs with mean sizes of 70, 200, 500 and 900 nm is administered to rats, the pharmacokinetic profiles are plotted based on semiquantification of the NE particles in blood by monitoring particle-bound fluorescence.

All NE groups are cleared from the blood rapidly in a size-dependent manner. Reductions in particle size lead to prolonged residence times in blood which indicates size-dependent effect on the circulation time. Live imaging reveals pervasive distribution of NEs throughout the body in rats with an apparent size-dependency. Ex vivo bioimaging demonstrates the dynamic biodistribution of NEs in different organs and tissues with different patterns.

The smallest NEs (70 nm) are prone to be taken up gradually by the liver, whereas the larger NEs are distributed in greater amounts in the spleen and lungs. The distribution in other tissues and organs is quite low. It is concluded that reductions in particle size lead to enhanced circulatory residence and hepatic exposure of NEs.

Keywords: Nanoemulsion, In vivo fate ,Pharmacokinetics, Biodistribution, Aggregation-caused quenching, Live imaging, Particle size.

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Article Information: Author links open overlay panelWufa Fan, Zhou Yu, Haixia Peng, Haisheng He, Yi Lu, Jianping Qi, Xiaochun Dong, Weili Zhao, Wei Wu; International Journal of Pharmaceutics, 2020.