title: In vitro uptake and transport studies of PEG-PLGA polymeric micelles in respiratory epithelial cells.
abstract: Polymeric micelles are considered promising carriers for pulmonary drug delivery. Their interaction with the respiratory epithelium, however, is mostly unknown. In the present study, methoxypoly (ethylene glycol) (mPEG)-poly (lactic-co-glycolic acid) (PLGA) micelles containing curcumin acetate (CA) or a mixture of CA and Nile Red (NR) were prepared using the solvent evaporation method. Calu-3 and NCI-H441 human respiratory epithelial cell monolayers were used as in vitro models of upper and lower respiratory tract epithelium barrier, respectively, to study the cellular uptake and transport of the vesicles. The results show that Calu-3 and NCI-H441 cells internalized micellar particles and that micelles were able to translocate across the cell monolayers. Micelles were more readily internalized into and permeated across Calu-3 cell monolayers when compared to NCI-H441 cells. Furthermore, the presence of inhibitors of endocytic processes, such as methyl-β-cyclodextrin, NaN3and hypertonic sucrose attenuated the cellular uptake and trafficking of micelles. In conclusion, this study demonstrated that mPEG-PLGA micelles translocate human respiratory epithelium in vitro through clathrin-, energy- and cholesterol-mediated endocytosis.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Yang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, 151 Malianwa North Road, Haidian District, Beijing 100193, China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Liu
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Carsten
authors.initials: C
authors.lastname: Ehrhardt
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, 151 Malianwa North Road, Haidian District, Beijing 100193, China. Electronic address: yhliao@implad.ac.cn.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Liao
mesh_terms: D001693:Biological Transport, Active; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004705:Endocytosis / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D008823:Micelles; D011091:Polyesters / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D008823:Micelles; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Biological barriers; Endocytosis; Micellar vesicles; Pulmonary drug delivery; Respiratory mucosa; Translocation