Puerarin-loaded PEG-PE micelles with enhanced anti-apoptotic effect and better pharmacokinetic profile

Drug Delivery

Jiang Zhang¹  Xinyi Liu²  Wenqun Li²  Jianhe Li²  Junyong Wu²  Daxiong Xiang²  Shilin Luo²  Jingjing Wang³ 

[1] College of Pharmacy, Changsha Medical College, Changsha, China;Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China;Institute of Clinical Pharmacy, Central South University, Changsha, China;School of Pharmaceutical Sciences, Central South University, Changsha, Chin;

关键词: PEG-PE micelles;    hemolysis;    pharmacokinetics;    cellular uptake;    apoptosis;   

DOI  :  10.1080/10717544.2018.1455763

来源: publisher

【 摘 要 】

Puerarin (PUE) is the most abundant isoflavonoid in kudzu root. It is widely used as a therapeutic agent for the treatment of cardiovascular diseases. However, the short elimination half-life, poor-bioavailability, and acute intravascular hemolysis of PUE are the main obstacles to its widespread clinical applications. Whereas PEG-PE micelles possess the ability to release medicine slowly, enhance the cellular uptake of drugs and improve their biocompatibility. Therefore, it was aim to fabricate puerarin-loaded PEG-PE (PUE@PEG-PE) micelles to improve the pharmaceutical properties of drugs. It can be observed from the TEM images that PUE@PEG-PE micelles appeared obvious core-shell structure and remained well-dispersed without aggregation and adhesion. PUE was successfully embedded in the core of PEG-PE micelles, which was confirmed by FT-IR and 1H NMR spectra. In vitro studies showed that PUE@PEG-PE micelles exhibited a sustained release behavior in pH 7.4 PBS buffer and decreased hemolysis rate of PUE. Compared with PUE, PUE@PEG-PE micelles showed a 3.2-fold increase in the half-life of PUE and a 1.58-fold increase in bioavailability. In addition, the PUE@PEG-PE micelles exerted enhanced protective effect against isoprenaline-induced H9c2 cells apoptosis compared with PUE, as evident by decreased percentage of Hoechst-positive cells, Caspase 3 activity, Bax expression, and increased Bcl-2 expression. Notably, the PEG-PE micelles exhibited favorable cellular uptake efficiency on H9c2 cells, and this may account for their enhanced anti-apoptotic effect of the incorporated drug. Altogether, the PUE@PEG-PE micelles were not only able to control the drug release but also offered promise to enhance the pharmacokinetic and pharmacodynamic potential of PUE.

【 授权许可】

CC BY