title: Preparation and characterization of a lovastatin-loaded protein-free nanostructured lipid carrier resembling high-density lipoprotein and evaluation of its targeting to foam cells.
abstract: This study was designed to investigate whether a non-protein nanostructured lipid carrier (NLC) resembling high-density lipoprotein (HDL) could deliver a hydrophobic anti-atherogenic drug, lovastatin, to foam cells. Lovastatin-loaded NLC (LT-NLC) was prepared by a nanoprecipitation/solvent diffusion method. The LT-NLC-apoprotein (LT-NLC-apo) was prepared by incubating LT-NLC with native HDL. The physicochemical parameters of LT-NLC were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and crystallization behavior. Targeting behavior and mechanism were demonstrated by the incubation of LT-NLC-apo with a RAW 264.7 macrophage-derived foam cell model in the presence or absence of very-low-density lipoprotein (VLDL) and lipase. The results showed that LT-NLC was solid spherical or oval in shape with an average diameter of 13.8 ± 2.2 nm, zeta potential of -29.3 ± 0.2 mV and entrapment efficiency of 96.2 ± 1.3%. Phagocytosis studies showed that uptake of LT-NLC-apo by macrophages was significantly lower than LT-NLC (p < 0.01), suggesting that LT-NLC-apo could possibly escape recognition from macrophages in vivo. The uptake was increased twofold when LT-NLC-apo was incubated with transfected foam cells containing VLDL and lipase. These results indicated that non-protein NLC resembling HDL could be a useful tool to deliver lipophilic anti-atherogenic drugs to foam cells, and that uptake could be enhanced by the VLDL receptor pathway.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing, Peoples Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Gu
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhang
authors.forename: Jianping
authors.initials: J
authors.lastname: Liu
authors.forename: John P
authors.initials: JP
authors.lastname: Shaw
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Shen
authors.forename: Yiming
authors.initials: Y
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Lu
authors.forename: Zimei
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000633:toxicity; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008148:Lovastatin / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D010587:Phagocytosis; D013678:Technology, Pharmaceutical / Q000379:methods*; D014162:Transfection; D020298:U937 Cells
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D004337:Drug Carriers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D008148:Lovastatin; D008049:Lipase