Resveratrol loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles for tail vein injection II: pharmacokinetics, tissue distribution and bioavailability

Mingfang Wu; Chen Zhong; Yiping Deng; Qian Zhang; Xiaoxue Zhang; Xiuhua Zhao

doi:10.1080/10717544.2019.1704944

Resveratrol loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles for tail vein injection II: pharmacokinetics, tissue distribution and bioavailability

Drug Deliv. 2020 Dec;27(1):81-90. doi: 10.1080/10717544.2019.1704944.

Authors

Mingfang Wu^{1

2}, Chen Zhong³, Yiping Deng^{1

2}, Qian Zhang^{1

2}, Xiaoxue Zhang^{1

2}, Xiuhua Zhao^{1

2}

Affiliations

¹ College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin, Heilongjiang, China.
² Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang, China.
³ State Key laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

Abstract

There are many kinds of biological activities of resveratrol itself, but its clinical application is limited by its poor solubility in water and low bioavailability. Therefore, we have prepared glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles (GL-HSA-RESNPs). The purpose of this study was to investigate the bioavailability, pharmacokinetics and tissue distribution of resveratrol in rats after single-dose tail vein injection administration of GL-HSA-RESNPs. A sensitive and reliable high performance liquid chromatography (HPLC) method was established to verify the content of resveratrol in rat plasma and organs. The C_max value after GL-HSA-RESNPs administration was significantly higher than that of resveratrol suspension (933 ± 76.64 ng/mL vs. 618 ± 42.54 ng/mL, p < .01). The T_max value obtained after GL-HSA-RESNPs administration was significantly shorter than that after resveratrol suspension administration (0.17 ± 0.01 h vs. 0.25 ± 0.01 h, p < .001). The bioavailability of GL-HSA-RESNPs was 4.25 times higher than that of the pure resveratrol. The concentration of resveratrol in the main organs of rats treated with the GL-HSA-RESNPs was higher than that in rats treated with the pure resveratrol. Rats treated with GL-HSA-RESNPs had the highest concentration of resveratrol in their liver. It is indicated that GL-HSA-RESNPs is a promising liver-targeted delivery system that improves the in vivo bioavailability of resveratrol.

Keywords: HPLC; Resveratrol; pharmacokinetics; tail vein administration; tissue distribution.

MeSH terms

Animals
Drug Carriers / chemistry*
Female
Glycyrrhizic Acid / chemistry*
Male
Metabolic Clearance Rate
Nanoparticles / chemistry*
Rats
Resveratrol / administration & dosage
Resveratrol / adverse effects
Resveratrol / pharmacokinetics*
Serum Albumin, Human / chemistry*
Solubility
Tissue Distribution

Substances

Drug Carriers
Glycyrrhizic Acid
Resveratrol
Serum Albumin, Human

Grants and funding

This work was supported by the Fundamental Research Funds for the Central Universities [2572018AA16] to M.W. and the Heilongjiang Touyan Innovation Team Program. C.Z. was sponsored by the Shanghai Talent Development funding.