Self-Assembled Nanoparticles from Xie-Bai-San Decoction: Isolation, Characterization and Enhancing Oral Bioavailability

Abstract

Background

Natural nanoparticles have been found to exist in traditional Chinese medicine (TCM) decoctions. However, whether natural nanoparticles can influence the oral bioavailability of active compounds has not been elucidated. Using Xie-Bai-San decoction (XBSD) as an example, the purpose of this study was to isolate, characterize and elucidate the mechanism of the nanoparticles (N-XBSD) in XBSD, and further to explore whether the bioavailability of the main active compounds could be enhanced by N-XBSD.

Methods

N-XBSD were isolated from XBSD, and investigated its characterization and study of its formation mechanism, and evaluation of its ability to enhance bioavailability of active compounds.

Results

The N-XBSD was successfully isolated with the average particle size of 104.53 nm, PDI of 0.27 and zeta potential of −5.14 mV. Meanwhile, all the eight active compounds were most presented in N-XBSD. Kukoamine B could self-assemble with mulberroside A or liquiritin to form nanoparticles, respectively. And the FT-IR and HRMS results indicated the possible binding of the ammonium group of kukoamine B with the phenolic hydroxyl group of mulberroside A or liquiritin, respectively. The established UPLC-MS/MS method was accurate and reliable and met the quantitative requirements. The pharmacokinetic behaviors of the N-XBSD and decoction were similar in rats. Most notably, compared to that of free drugs, the C_max, AUC_0-∞, AUC_0-t, T_1/2 and MRT_0-∞ values of index compounds were the higher in N-XBSD, with a slower plasma clearance rate in rats.

Conclusion

The major active compounds of XBSD were mainly distributed in N-XBSD, and N-XBSD was formed through self-assembly among active compounds. N-XBSD could obviously promote the bioavailability of active compounds, indicating natural nanoparticles of decoctions play an important role in therapeutic effects.

Graphical Abstract

Keywords:

• nanoparticles
• enhancing bioavailability
• comparative pharmacokinetics
• UPLC-MS/MS
• Xie-Bai-San decoction

Abbreviations

AUC_0-t, area under curve from time zero to time t; AUC_0-∞, area under curve from time zero to time infinity; C_max, maximum plasma concentration; CLz/F, clearance corrected for bioavailability; FT-IR, Fourier transform infrared spectroscopy; HPLC, high-performance liquid chromatography; HRMS, high-resolution mass spectrometry; IS, internal standard; LOQ, limit of quantification; MRT_0-t, mean residence time from time zero to time t; SCF, simulated colonic fluid; SGF, simulated gastric fluid; SIF, simulated intestinal fluid; TCM, traditional Chinese medicine; T_1/2, terminal elimination half-life; T_max, time to reach C_max; TEM, transmission electron microscopy; UPLC-MS/MS, ultra-performance liquid chromatography-tandem mass spectrometry.

Data Sharing Statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

All animal experimental protocols were approved by the Institutional Animal Care and Use Committee of Shanghai University of Traditional Chinese Medicine (PZSHUTCM220725022). All experiments were performed in accordance with the Guidelines for Care and Use of Laboratory Animals of Shanghai University of Traditional Chinese Medicine.

Acknowledgments

This study was supported by “Shuguang Program” supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission [grant numbers 20SG43]; Program of Shanghai Academic/Technology Research Leader (grant 22XD1423000); Programs of the National Natural Science Foundation of China [grant number 82274066 and 82204777]; Project from Shanghai Collaborative Innovation Center of Industrial Transformation of Hospital TCM Preparation [grant number 20S21902500]; Shanghai Science and Technology Innovation Project [grant number 18401930600]; Program from the Shanghai Committee of Science and Technology [grant number 18401930600 and 21010504200]; Youth Talent Program from the Shanghai Municipal Health Commission (grant 2022YQ030); National Key Research and Development Program of China (grant 2022YFC3501705); the Innovation activity plan for College Students of SHUTCM [grant number 2020SHUTCM131]; Shanghai Zhangjiang National Independent Innovation Demonstration Zone Special Development Fund Major Project[grant number ZJ2022-ZD-009].

Disclosure

The authors report no conflicts of interest in this work.