This study is one of the first to test the relationship of formulation and structure of reconstituted high density lipoproteins (rHDL), drug behavior involved in remolding process and their targeting mechanism in a foam cell model. Tanshinone IIA-loaded rHDL (TA-rHDL) with different formulations and techniques were prepared and characterized. The targeting mechanism and drug behavior involved in remolding process were undertaken using a foam cell model. TA-rHDL prepared with cholesteryl ester (CE) and glycerol trioleate (TG) were spheres, or else discs. Guanidine hydrochloride denaturation experiments showed increased stability with TA-rHDL, compared to free apos. Phagocytosis tests demonstrated that the spherical TA-rHDL had 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. Lipophilic Tanshinone IIA could be re-entrapped in rHDL after remolding from discs to spheres and uptaken more by foam cells. Discoidal rHDL may serve as potential nanocarriers for targeting lipophilic cardiovascular drugs to atherosclerosis plaque.
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