Abstract: Three longcirculating nanostructured lipid carriers loaded with artemisinin (ART) were prepared with polyethyleneglycol stearate of different polymerization degree (PEG_n-SA, n=25,40,55) by the high pressure homogenization method.The in vitro drug release,phagocytic uptake by J774 cells and fixed aqueous layer thickness (FALT) of nanostructured lipid carriersloaded with ART (ART-NLC) and three PEGylated nanostructured lipid carriers loaded with ART (PEG_n-ART-NLC, n=25,40,55) were examined and compared.The profiles of ART release from ART-NLC and PEG_n-ART-NLC were studied at pH7.4 with or without human plasma by high-performance liquid chromatography with post-column derivatization and UV detection.The ART release from PEG_n-ART-NLC increased as the increasing of polymerization degree of polyethyleneglycol (PEG).When plasma was added in release media,the ART in vitro releasing from NLCs was remarkably upregulated. On the contrary,ART release was reduced as the increasing of polymerization degree of PEG.The ART in vitro phagocytic uptakes of PEG_n-ART-NLCs by J774 cells were significantly lower than that of ART-NLC.ART phagocytic uptake by J774 cells increased as the increasing of polymerization degree of PEG or incubation time.Human plasma can noticeably up-regulate ART phagocytic uptake by J774 cells.The FALTs of ART-NLC and three PEG_n-ART-NLC (n=25,40,55) were 0.31 nm,1.76 nm,1.86 nm and 2.04 nm,respectively.These results suggested that the prepared artemisinin PEGylated nanostructured lipid carriers exhibited sustained release and anti-phagocytic uptake characteristics.

Key words: artemisinin, nanostructured lipid carriers, long-circulating, in vitro release, phagocytic uptake