Improved uptake and bioavailability of cinnamaldehyde via solid lipid nanoparticles for oral delivery

Abstract

Objective

The purpose of this experiment was to explore the effect of Solid lipid nanoparticles (SLNs) on improving the oral absorption and bioavailability of cinnamaldehyde (CA).

Methods

CA-SLNs were prepared by high-pressure homogenization and characterized by particle size, entrapment efficiency, and morphology, thermal behavior and attenuated total reflection Fourier transform infrared (ATR-FTIR). In vitro characteristics of release, stability experiments, cytotoxicity, uptake and transport across Caco-2 cell monolayer of CA-SLNs were studied as well. In addition, CA-SLNs underwent pharmacokinetic and gastrointestinal mucosal irritation studies in rats.

Results

CA-SLNs exhibited a spherical shape with a particle size of 44.57 ± 0.27 nm, zeta potential of −27.66 ± 1.9 mV and entrapment efficiency of 83.63% ± 2.16%. Differential scanning calorimetry (DSC) and ATR-FTIR confirmed that CA was well encapsulated. In vitro release of CA-SLNs displayed that most of the drug (90.77% ± 5%) was released in the phosphate buffer, and only a small amount of drug (18.55% ± 5%) was released in the HCl buffer. CA-SLNs were taken up by an energy-dependent, endocytic mechanism mediated by caveolae mediated endocytosis across Caco-2 cells. The CA permeation through Caco-2 cell was facilitated by CA-SLNs. The outcome of the gastrointestinal irritation test demonstrated that CA-SLNs had no irritation to the rats’ intestines. Compared with CA dispersions, incorporation of SLNs increased the oral bioavailability of CA more than 1.69-fold.

Conclusions

It was concluded that CA-SLNs improved the absorption across Caco-2 cell model and improved the oral administration bioavailability of CA in rats.

Graphical Abstract

Keywords:

• Cinnamaldehyde
• solid lipid nanoparticles
• cellular uptake
• in vivo pharmacokinetics

Acknowledgements

The authors gratefully acknowledge the financial support from National Natural Science Foundations of China (No. 81803831, 81873019), Key University natural science research project of Anhui province (KJ2018A0301). The authors also express special thanks to Dr. Xiaoqin Chu for her expert opinion and advice.

Disclosure statement

The authors declare that they have no conflict of interest.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (No. 81803831) and Anhui Provincial Major Science and Technology Project (201903a07020007).