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Preparation and evaluation of self-microemulsions for improved bioavailability of ginsenoside-Rh1 and Rh2

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Abstract

Due to intestinal cytochrome P450 (CYP450)-mediated metabolism and P-glycoprotein (P-gp) efflux, poor oral bioavailability hinders ginsenoside-Rh1 (Rh1) and ginsenoside-Rh2 (Rh2) from clinical application. In this study, Rh1 and Rh2 were incorporated into two self-microemulsions (SME-1 and SME-2) to improve oral bioavailability. SME-1 contained both CYP450 and P-gp inhibitory excipients while SME-2 only consisted of P-gp inhibitory excipients. Results for release, cellular uptake, transport, and lymph node distribution demonstrated no significant difference between either self-microemulsions in vivo, but were elevated significantly in comparison to the free drug. The pharmaceutical profiles in vivo showed that the bioavailability of Rh1 in SME-1 (33.25%) was significantly higher than that in either SME-2 (21.28%) or free drug (12.92%). There was no significant difference in bioavailability for Rh2 between SME-1 (48.69%) or SME-2 (41.73%), although they both had remarkable increase in comparison to free drug (15.02%). We confirmed that SME containing CYP450 and P-gp inhibitory excipient could distinctively improve the oral availabilities of Rh1 compared to free drug or SME containing P-gp inhibitory excipient. No notable increase was observed between either SME for Rh2, suggesting that Rh2 undergoes P-gp-mediated efflux, but may not undergo distinct CYP450-mediated metabolism.

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Abbreviations

Rh1:

ginsenoside-Rh1

Rh2:

ginsenoside-Rh2

CYP450:

cytochromes P450

SME:

self-microemulsion

AUC:

area under the curve

MEM:

minimum essential medium

NEAA:

non-essential amino acid

FBS:

fetal bovine serum

TEER:

transepithelial electrical resistance

SPF:

specific pathogen free

DOS-1227:

dammarane oligosaponins

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81603052), the Beijing Natural Science Foundation (Grant No. 7164280), the CAMS Initiative for Innovative Medicine (CAMS-I2M, Grant No. 2016-I2M-2-006), and the Key Laboratory for Neurodegenerative Diseases (Capital Medical University), Ministry of Education (Grant No. 2015SJBX03).

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Authors and Affiliations

  1. Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing, 100193, P. R. China

    Feifei Yang, Jing Zhou, Chunyu Liu, Ruile Pan, Qi Chang, Xinmin Liu & Yonghong Liao

  2. Key Laboratory for Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, 100054, China

    Xiao Hu

  3. Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Stephanie Kyoungchun Yu

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  1. Feifei Yang
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  2. Jing Zhou
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  3. Xiao Hu
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  4. Stephanie Kyoungchun Yu
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  7. Qi Chang
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  9. Yonghong Liao
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Correspondence to Yonghong Liao.

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The authors declare that they have no conflict of interest.

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Yang, F., Zhou, J., Hu, X. et al. Preparation and evaluation of self-microemulsions for improved bioavailability of ginsenoside-Rh1 and Rh2. Drug Deliv. and Transl. Res. 7, 731–737 (2017). https://doi.org/10.1007/s13346-017-0402-7

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