Nanostructured lipid carriers constituted from high-density lipoprotein components for delivery of a lipophilic cardiovascular drug.

To investigate the possibility of reconstituted protein-free high-density lipoprotein (HDL) being a carrier for delivering a lipophilic cardiovascular drug, Tanshinone IIA-loaded HDL-like nanostructured lipid carriers (TA-NLC) were prepared by a nanoprecipitation/solvent diffusion method. The physicochemical parameters of TA-NLC were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, differential scanning calorimetry (DSC) and stability. A novel two-step method has been employed to determine entrapment efficiency of TA-NLC. The binding properties of TA-NLC to apolipoproteins were investigated by in vitro incubation competition assay in the presence of native HDL and electrophoresis test. Phagocytosis and cytotoxicity was evaluated using mouse macrophage cell line RAW 264.7 with TA-NLC and incubated TA-NLC with native HDL (TA-NLC-apo). The results showed that TA-NLC had an average diameter of 8.0+/-1.2 nm, zeta potential of -29.0+/-0.0 mV, drug loading of 6.17+/-0.3% and entrapment efficiency of 97.84+/-1.2%. TA-NLC were demonstrated spheres with drug incorporated in lipid core forming a shell-core structure. DSC analysis showed that TA was dispersed in NLC in an amorphous state. The incorporation of glycerol trioleate to NLC led to crystal order disturbance. Agarose gel electrophoresis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-SPAGE) patterns indicated that TA-NLC could bind to apolipoprotein A-I (apoA-I) specifically in vitro. Phagocytosis studies showed significant differences in uptake between TA-NLC and TA-NLC-apo and demonstrated that TA-NLC incubated with native HDL could turn endogenous by association to apolipoproteins, which cannot trigger immunological responses and could escape from recognition by macrophages. Copyright (c) 2010 Elsevier B.V. All rights reserved.