Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation, characterization, plasma, and kidney pharmacokinetics

Abstract

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6 ± 5.95 nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71 ± 3.02%, and the drug loading was 1.56 ± 0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC_kidney/AUC_plasma = 0.586 ± 0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.

Keywords:

• Kidney bioavailability
• nanoparticles
• microdialysis
• pharmacokinetics
• rhein

Acknowledgements

We would like to thank Matthew Thomas Haynes, Division of Molecular Pharmaceuticsand Center of Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill for his kind assistance in using the PhonenixWinnonlin 6.3 software.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This project was financially supported by the National Natural Science Foundation of China [No. 81373982] and the Natural Science Foundation of Zhejiang Province [No. LY13H280007].