The contribution of absorption of integral nanocrystals to enhancement of oral bioavailability of quercetin

• 作者: Baode Shen Chengying Shen Weifeng Zhu Hailong Yuan
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（4）
• 所属期刊栏目: Original articles
• 页码范围: 978-988
• 页数: 11页
• 语种: 英文

摘要

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 expo-sure 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 accumu-lation 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 dis-solves faster in vivo,leading to higher distribution of QT(146.90 vs.117.91 h·μg/mL)but lower accu-mulation 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 nanocrys-tals(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 abso-lute 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 ob-tained.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 enhance-ment.