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

Xin Jin,^1,2 Zhen-hai Zhang,¹ E Sun,¹ Qian Qian,¹ Xiao-bin Tan,¹ Xiao-bin Jia<sup>1

1</sup>Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, ²College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China

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