Original articles
Baode Shen, Chengying Shen, Weifeng Zhu, Hailong Yuan. The contribution of absorption of integral nanocrystals to enhancement of oral bioavailability of quercetin[J]. Acta Pharmaceutica Sinica B, 2021, 11(4): 978-988

The contribution of absorption of integral nanocrystals to enhancement of oral bioavailability of quercetin
Baode Shena,b, Chengying Shena, Weifeng Zhub, Hailong Yuana
a Department of Pharmacy, Air Force Medical Center, PLA, Beijing 100142, China;
b Key Lab of Modern Preparation of Traditional Chinese Medicine(TCM), Ministry of Education, Jiangxi University of TCM, Nanchang 330004, China
Abstract:
In this study, self-discriminating hybrid nanocrystals was utilized to explore the biological fate of quercetin hybrid nanocrystals (QT-HNCs) with diameter around 280 nm (QT-HNCs-280) and 550 nm (QT-HNCs-550) following oral and intravenous administration and the contribution of integral nanocrystals to oral bioavailability enhancement of QT was estimated by comparing the absolute exposure of integral QT-HNCs and total QT in the liver. Results showed that QT-HNCs could reside in vivo as intact nanocrystals for as long as 48 h following oral and intravenous administration. A higher accumulation of integral QT-HNCs in liver and lung was observed for both oral and intravenous administration of QT-HNCs. The particle size affects the absorption and biodistribution of integral QT-HNCs and total QT. As compared to QT-HNCs-550, QT-HNCs-280 with smaller particle size is more easily absorbed, but dissolves faster in vivo, leading to higher distribution of QT (146.90 vs. 117.91 h·μg/mL) but lower accumulation of integral nanocrystals (6.8 2e10 vs. 15.27e10 h·[p/s]/[μW/cm2]) in liver following oral administration. Due to its slower dissolution and enhanced recognition by RES, QT-HNCs-550 with larger diameter shows higher liver distribution for both of QT (1015.80 h·μg/mL) and integral nanocrystals (259.63e10 h·[p/s]/[μW/cm2]) than those of QT-HNCs-280 (673.82 & 77.66e10 h·[p/s]/[μW/cm2]) following intravenous administration. The absolute exposure of integral QT-HNCs in liver following oral administration of QT-HNCs are 8.78% for QT-HNCs-280 and 5.88% for QT-HNCs-550, while the absolute exposure of total QT for QT-HNCs-280 and QT-HNCs-550 are 21.80% and 11.61%, respectively. Owing to imprecise quantification method, a surprisingly high contribution of integral QT-HNCs to oral bioavailability enhancement of QT (40.27% for QT-HNCs-280 and 50.65% for QT-HNCs-550) was obtained. These results revealed significant difference in absorption and biodistrbution between integral nanocrystals and overall drugs following oral and intravenous administration of QT-HNCs, and provided a meaningful reference for the contribution of integral nanocrystals to overall bioavailability enhancement.
Key words:    Nanocrystals    Biological fate    Quercetin    Pharmacokinetics    Biodistribution    Oral bioavailability    Contribution    Drug delivery   
Received: 2020-11-16     Revised: 2020-12-27
DOI: 10.1016/j.apsb.2021.02.015
Funds: This work was supported by the National Natural Science Foundation of China (Nos. 81803741 and 81873092).
Corresponding author: Weifeng Zhu, zwf0322@126.com;Hailong Yuan, yhlpharm@126.com     Email:zwf0322@126.com;yhlpharm@126.com
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Baode Shen
Chengying Shen
Weifeng Zhu
Hailong Yuan

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