title: Human Airway Primary Epithelial Cells Show Distinct Architectures on Membrane Supports Under Different Culture Conditions.
abstract: To facilitate drug development for lung delivery, it is highly demanding to establish appropriate airway epithelial cell models as transport barriers to evaluate pharmacokinetic profiles of drug molecules. Besides the cancer-derived cell lines, as the primary cell model, normal human bronchial epithelial (NHBE) cells have been used for drug screenings because of physiological relevance to in vivo. Therefore, to accurately interpret drug transport data in NHBE measured by different laboratories, it is important to know biophysical characteristics of NHBE grown on membranes in different culture conditions. In this study, NHBE was grown on the polyester membrane in a different medium and its transport barrier properties as well as cell architectures were fully characterized by functional assays and confocal imaging throughout the days of cultures. Moreover, NHBE cells on inserts in a different medium were subject to either of air-interfaced culture (AIC) or liquid-covered culture (LCC) condition. Cells in the AIC condition were cultivated on the membrane with medium in the basolateral side only, whereas cells with medium in apical and basolateral sides under the LCC condition. Quantitative microscopic imaging with biophysical examination revealed distinct multilayered architectures of differentiated NHBE cells, suggesting NHBE as functional cell barriers for the lung-targeting drug transport.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju, Gyeongnam, 52828, Republic of Korea.|Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church St., Ann Arbor, MI, 48109, USA.
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Min
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church St., Ann Arbor, MI, 48109, USA.
authors.forename: Gus R
authors.initials: GR
authors.lastname: Rosania
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju, Gyeongnam, 52828, Republic of Korea. shinmc@gnu.ac.kr.
authors.forename: Meong Cheol
authors.initials: MC
authors.lastname: Shin
mesh_terms: D000388:Air; D018929:Cell Culture Techniques / Q000379:methods*; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008567:Membranes, Artificial; D010539:Permeability; D016062:Porosity; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: D003470:Culture Media; D008567:Membranes, Artificial
keywords: Airway epithelial cell; Differentiation; Drug transport; NHBE; Porous membrane; Tight junction
references.citation: Eur Respir J. 1997 Oct;10(10):2398-403
references.pmid: 9387971
references.citation: J Drug Target. 2003 Jan;11(1):61-74
references.pmid: 12852442
references.citation: Adv Drug Deliv Rev. 2006 Oct 31;58(9-10):1030-60
references.pmid: 17010473
references.citation: In Vitro Cell Dev Biol Anim. 1998 Jun;34(6):478-81
references.pmid: 9661051
references.citation: Eur J Pharm Sci. 2002 May;15(4):331-40
references.pmid: 11988394
references.citation: J Control Release. 2003 Feb 21;87(1-3):131-8
references.pmid: 12618029
references.citation: J Biol Chem. 1998 Nov 6;273(45):29745-53
references.pmid: 9792688
references.citation: J Aerosol Med. 2005 Summer;18(2):137-82
references.pmid: 15966771
references.citation: Biotechniques. 2005 Aug;39(2):249-55
references.pmid: 16116798
references.citation: Adv Drug Deliv Rev. 1998 Aug 3;33(1-2):15-30
references.pmid: 10837650
references.citation: Pharm Res. 1999 May;16(5):601-8
references.pmid: 10349999
references.citation: Int J Pharm. 2003 May 12;257(1-2):161-7
references.pmid: 12711171
references.citation: Pharm Sci Technolo Today. 2000 Jan;3(1):18-27
references.pmid: 10637597
references.citation: Am J Physiol. 1996 Dec;271(6 Pt 1):L1023-8
references.pmid: 8997274
references.citation: Acta Otolaryngol. 2000 Oct;120(8):944-9
references.pmid: 11200589
references.citation: J Clin Invest. 1998 Sep 15;102(6):1125-31
references.pmid: 9739046
references.citation: J Pharm Sci. 2007 Feb;96(2):341-50
references.pmid: 17080426
references.citation: J Muscle Res Cell Motil. 2001;22(3):229-42
references.pmid: 11763195
references.citation: J Pharm Pharmacol. 2009 Mar;61(3):293-301
references.pmid: 19222901
references.citation: Eur J Pharm Sci. 2013 Aug 16;49(5):805-18
references.pmid: 23797056
references.citation: Am J Respir Cell Mol Biol. 1996 Jan;14(1):104-12
references.pmid: 8534481
references.citation: Am J Physiol. 1995 Sep;269(3 Pt 1):L377-87
references.pmid: 7573472
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Jun;278(6):L1118-28
references.pmid: 10835316
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Aug;285(2):L427-33
references.pmid: 12851213
references.citation: Pharm Res. 1995 Oct;12(10):1499-505
references.pmid: 8584489
references.citation: Eur J Pharm Biopharm. 2005 Jul;60(2):193-205
references.pmid: 15939233
references.citation: In Vitro Cell Dev Biol Anim. 2003 May-Jun;39(5-6):213-20
references.pmid: 14613331
references.citation: Pharm Res. 2006 Jul;23 (7):1482-90
references.pmid: 16779708
references.citation: Biochem Soc Trans. 2009 Aug;37(Pt 4):877-81
references.pmid: 19614611
references.citation: Pharm Res. 2003 Oct;20(10):1690-6
references.pmid: 14620527
references.citation: Toxicology. 2001 Mar 7;160(1-3):35-46
references.pmid: 11246122
references.citation: Eur Respir J. 2000 Jun;15(6):1058-68
references.pmid: 10885425
references.citation: Eur J Pharm Sci. 2004 Dec;23(4-5):385-91
references.pmid: 15567292
references.citation: Eur Arch Otorhinolaryngol. 2003 Jul;260(6):325-30
references.pmid: 12883958
references.citation: Nat Protoc. 2006;1(1):357-62
references.pmid: 17406256
references.citation: In Vitro Cell Dev Biol Anim. 2003 Jan-Feb;39(1-2):56-62
references.pmid: 12892528
references.citation: Acta Biomater. 2010 Mar;6(3):1191-9
references.pmid: 19716445
references.citation: Am J Respir Cell Mol Biol. 2005 Apr;32(4):281-9
references.pmid: 15640437
references.citation: Am J Respir Cell Mol Biol. 2012 Sep;47(3):280-7
references.pmid: 22312018
references.citation: J Aerosol Med. 2002 Summer;15(2):131-9
references.pmid: 12184863
references.citation: Mol Cell Biol. 1998 Nov;18(11):6666-78
references.pmid: 9774681
references.citation: Am Ind Hyg Assoc J. 1980 Jun;41(6):399-409
references.pmid: 7395753