title: Cellular uptake and elimination of lipophilic drug delivered by nanocarriers.
abstract: To investigate the cellular uptake and elimination process of a lipophilic drug loaded in different nanocarriers, emulsions, liposomes and poly (DL-lactide-co-glycolide) (PLGA) nanoparticles loaded with a model drug, coumarin 6, were prepared and their transportation in HeLa cells compared. After 4 h incubation, liposomes and nanoparticles mediated significantly higher intracellular drug levels, which were 3 or 2.5 times that of the emulsion group, into cells. A novel kinetic model was established to analyze the cellular elimination process. Emulsions had the longest intracellular mean residence time (MRT), which was about 1-2 times longer than other nanocarriers. The endocytosis inhibition experiment suggested that the coumarin 6 in liposomes and nanoparticles entered cells directly via diffusion, while part of the intracellular coumarin 6 was taken up through clathrin-mediated endocytosis in emulsions. Combined with the results on uptake pathway and kinetic parameters, it can be concluded that different nanocarriers bring about diverse mechanisms of cellular uptake and elimination.
authors.affiliation: Institute of Pharmaceutics, Zhejiang University, Hangzhou, Zhejiang, P. R. China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Sun
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenquan
authors.initials: W
authors.lastname: Liang
mesh_terms: D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions; D005456:Fluorescent Dyes; D006367:HeLa Cells; D006801:Humans; D007211:Indoles; D008081:Liposomes / Q000737:chemistry*; D018613:Microscopy, Confocal; D010316:Particle Size
chemical_list: D000925:Anticoagulants; D003374:Coumarins; D004337:Drug Carriers; D004655:Emulsions; D005456:Fluorescent Dyes; D007211:Indoles; D008081:Liposomes; C007293:DAPI; C030123:coumarin