Preparation of a nanoscale baohuoside I-phospholipid complex and determination of its absorption: in vivo and in vitro evaluations

Abstract

Background

Baohuoside I is a potential anticancer drug for a variety of malignancies and has been approved for in vitro use. However, baohuoside I has very poor oral absorption.

Methods

In the present study, we prepared baohuoside I-phospholipid complexes of different diameters and determined their physicochemical properties using transmission electron microscopy, ultraviolet spectroscopy, and differential scanning calorimetry. The in vitro absorption of baohuoside I and baohuoside I-phospholipid complexes of different sizes were compared using the Caco-2 cell culture model, and subsequently, the bioavailability of baohuosidel and its complexes were estimated in vivo.

Results

Compared with the large-sized phospholipid complexes, a nanoscale phospholipid complex improved the oral bioavailability of baohuoside I. In addition, our results suggest that the smaller the particle size, the faster the complexes crossed the Caco-2 monolayer and the faster they were resorbed after oral administration in rats. The relative oral bioavailability of a nanoscale size 81 ± 10 nm baohuoside I-phospholipid complex (area under the concentration-time curve [AUC]^0–∞) was 342%, while that of baohuoside I and a 227.3 ± 65.2 μm baohuoside I-phospholipid complex was 165%.

Conclusion

We enhanced the oral bioavailability of baohuoside I by reducing the particle size of the phospholipid complex to the nanometer range, thereby improving its potential for clinical application.

Keywords:

• nanoscale phospholipid complex
• Caco-2 cell monolayer
• bioavailability
• oral absorption

Acknowledgments

This work was supported by the National Natural Science Foundation of China (30572372 and 30973944) and the Open Project of Key Laboratory of Oral Drug Delivery System of the State Administration of Traditional Chinese Medicine (2011 NDDCM01001). The authors thank Hu Ming from Washington State University for gifting the Caco-2 TC7 cell line.

Disclosure

The authors report no conflicts of interest in this work.