PMID: 22570939May 11, 2012Paper

Tanshinone IIA-loaded reconstituted high density lipoproteins: Atherosclerotic plaque targeting mechanism in a foam cell model and pharmacokinetics in rabbits

Die Pharmazie
Wenli ZhangJi Wang

Abstract

Spherical and discoidal tanshinone IIA-loaded reconstituted high density lipoproteins (TA-rHDL) with different formulations and techniques were prepared and characterized. The targeting mechanism was investigated using a foam cell model. Pharmacokinetics of four TA-rHDL formulations with or without apolipoproteins (apos) after a single dose intravenous injection to rabbits has been studied. The results showed that the sizes of spherical and discoidal TA-rHDL increased after coupling with apos from 55.38 nm to 157.26 nm, 61.03 nm to 166.19 nm, and zeta potential decreased from -29.2 mV to -35.4 mV, -5.2 mV to -11.82 mV, respectively. The results of circular dichroic spectroscopy indicated variations of apos in protein secondary structure after binding with lipids. Phagocytosis tests demonstrated that the spherical TA-rHDL had a targeting effect for foam cells through the scavenger receptor-BI and CE-TG interchange with TG-rich lipoproteins pathway under cholesteryl ester transfer protein. Discoidal TA-rHDL could reconstruct to spheres and target via a similar route as TA-rHDL spheres, showing a higher targeting efficiency. In vivo experiments showed that areas under the plasma level-time curve (AUC) of TA increased as a function...Continue Reading

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.