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 of spherical and discoidal rHDL, which were 4 and 13 times more than that of TA suspensions, respectively. Spherical and discoidal TA-rHDL had long circulating times in blood with mean residence time (MRT) of 15.874 and 18.956h, respectively, compared to 1.802h of TA suspensions, 14.190h of spherical TA-rHDL without apos and 15.071 of discoidal TA-rHDL without apos. The distribution volume of spherical TA-rHDL was 2.143 and 1.552 times as that of discoidal TA-rHDL and TA suspensions, respectively. In conclusion, TA-rHDL may be a long-circulating, healthy and potentially targeted carrier for delivering lipophilic cardiovascular drugs.

Links

Publisher Full Text

Authors

Zhang W, Li J, Liu J, Wu Z, Xu Y, Wang J

Institution

Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.

Source

Die Pharmazie 67:4 2012 Apr pg 324-30

MeSH

Animals
Apolipoproteins
Cardiovascular Agents
Cell Line
Circular Dichroism
Diterpenes, Abietane
Drug Carriers
Drug Delivery Systems
Electrochemistry
Foam Cells
Infusions, Parenteral
Lipoproteins, HDL
Liposomes
Male
Mice
Models, Biological
Nanoparticles
Particle Size
Phagocytosis
Plaque, Atherosclerotic
Plasmids
Rabbits
Reproducibility of Results
Transfection

Pub Type(s)

In Vitro
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22570939