{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:46:59Z","timestamp":1789994819287,"version":"4.0.1"},"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2013,2,27]],"date-time":"2013-02-27T00:00:00Z","timestamp":1361923200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0057136","type":"journal-article","created":{"date-parts":[[2013,2,27]],"date-time":"2013-02-27T23:10:58Z","timestamp":1362006658000},"page":"e57136","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":44,"title":["Permeation of Insulin, Calcitonin and Exenatide across Caco-2 Monolayers: Measurement Using a Rapid, 3-Day System"],"prefix":"10.1371","volume":"8","author":[{"given":"Vivek","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishit","family":"Doshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Mitragotri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,2,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrd1695","article-title":"Protein drug stability: a formulation challenge","volume":"4","author":"S Frokjaer","year":"2005","journal-title":"Nat Rev Drug Discov"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v20.i23.30","article-title":"Emerging trends in oral delivery of peptide and protein drugs","volume":"20","author":"RI Mahato","year":"2003","journal-title":"Crit Rev Ther Drug Carrier Syst"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jconrel.2004.04.013","article-title":"Oral delivery of macromolecules using intestinal patches: applications for insulin delivery","volume":"98","author":"K Whitehead","year":"2004","journal-title":"J Control Release"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S0167-7799(97)01170-0","article-title":"Innovative strategies for the oral delivery of drugs and peptides","volume":"16","author":"A Fasano","year":"1998","journal-title":"Trends Biotechnol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2165\/00063030-200519030-00003","article-title":"Oral delivery of peptide drugs: barriers and developments","volume":"19","author":"JH Hamman","year":"2005","journal-title":"BioDrugs"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1007\/BF02976925","article-title":"Protein drug oral delivery: the recent progress","volume":"25","author":"HJ Lee","year":"2002","journal-title":"Arch Pharm Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.drudis.2006.08.005","article-title":"Is the oral route possible for peptide and protein drug delivery?","volume":"11","author":"M Morishita","year":"2006","journal-title":"Drug Discov Today"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1177\/026119290102900604","article-title":"In vitro models of the intestinal barrier. The report and recommendations of ECVAM Workshop 46. European Centre for the Validation of Alternative methods","volume":"29","author":"E Le Ferrec","year":"2001","journal-title":"Altern Lab Anim"},{"key":"ref9","first-page":"27","article-title":"Caco-2 monolayers in experimental and theoretical predictions of drug transport","volume":"46","author":"P Artursson","year":"2001","journal-title":"Adv Drug Deliv Rev"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/S0016-5085(89)80072-1","article-title":"Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability","volume":"96","author":"IJ Hidalgo","year":"1989","journal-title":"Gastroenterology"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1023\/A:1015937605100","article-title":"Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa","volume":"7","author":"AR Hilgers","year":"1990","journal-title":"Pharm Res"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1038\/nprot.2007.303","article-title":"Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers","volume":"2","author":"I Hubatsch","year":"2007","journal-title":"Nat Protoc"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1023\/A:1012112820371","article-title":"Evaluation of Biocoat intestinal epithelium differentiation environment (3-day cultured Caco-2 cells) as an absorption screening model with improved productivity","volume":"14","author":"S Chong","year":"1997","journal-title":"Pharm Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1023\/A:1016082829111","article-title":"Comparison of HT29-18-C1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption","volume":"13","author":"A Collett","year":"1996","journal-title":"Pharm Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0378-5173(00)00334-3","article-title":"Development of a more rapid, reduced serum culture system for Caco-2 monolayers and application to the biopharmaceutics classification system","volume":"200","author":"KA Lentz","year":"2000","journal-title":"Int J Pharm"},{"key":"ref16","first-page":"1","article-title":"Comparison of the BD BioCoat\u2122 Intestinal Epithelial Environment with the Conventional 21-Day Caco-2 System","volume":"416","author":"D Asa","year":"2008","journal-title":"BD Biosciences Technical Bulletin"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1002\/jps.10050","article-title":"New and better protocols for a short-term Caco-2 cell culture system","volume":"91","author":"S Yamashita","year":"2002","journal-title":"J Pharm Sci"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0014-5793(93)81758-R","article-title":"Regulation of c-myc expression by sodium butyrate in the colon carcinoma cell line Caco-2","volume":"326","author":"A Souleimani","year":"1993","journal-title":"FEBS Lett"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/10611860400020191","article-title":"Tetradecylmaltoside (TDM) enhances in vitro and in vivo intestinal absorption of enoxaparin, a low molecular weight heparin","volume":"13","author":"T Yang","year":"2005","journal-title":"J Drug Target"},{"key":"ref20","first-page":"489","article-title":"Insulin therapy for type 2 diabetes: rescue, augmentation, and replacement of beta-cell function","volume":"70","author":"JA Mayfield","year":"2004","journal-title":"Am Fam Physician"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2165\/00024677-200403020-00006","article-title":"Calcitonin therapy in osteoporosis","volume":"3","author":"M Munoz-Torres","year":"2004","journal-title":"Treat Endocrinol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/nrd1828","article-title":"Exenatide","volume":"4","author":"MB Davidson","year":"2005","journal-title":"Nat Rev Drug Discov"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0928-0987(97)10019-7","article-title":"Estimation of permeability by passive diffusion through Caco-2 cell monolayers using the drugs&apos; lipophilicity and molecular weight","volume":"6","author":"G Camenisch","year":"1998","journal-title":"Eur J Pharm Sci"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/(SICI)1520-6017(200001)89:1<63::AID-JPS7>3.0.CO;2-6","article-title":"Caco-2 versus Caco-2\/HT29-MTX co-cultured cell lines: permeabilities via diffusion, inside- and outside-directed carrier-mediated transport","volume":"89","author":"C Hilgendorf","year":"2000","journal-title":"J Pharm Sci"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1471-2121-7-20","article-title":"Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2\/HT29-5M21)","volume":"7","author":"G Nollevaux","year":"2006","journal-title":"BMC Cell Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/jbm.a.10128","article-title":"Novel complexation hydrogels for oral peptide delivery: in vitro evaluation of their cytocompatibility and insulin-transport enhancing effects using Caco-2 cell monolayers","volume":"67","author":"H Ichikawa","year":"2003","journal-title":"J Biomed Mater Res A"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1111\/j.1745-7254.2006.00424.x","article-title":"In vitro and in vivo evaluation of a novel oral insulin formulation","volume":"27","author":"EL Ma","year":"2006","journal-title":"Acta Pharmacol Sin"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1007\/s11095-010-0345-x","article-title":"Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by Caco-2 cells--towards oral insulin","volume":"28","author":"C Thompson","year":"2011","journal-title":"Pharm Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jconrel.2005.05.016","article-title":"Enhanced intestinal absorption of salmon calcitonin (sCT) from proliposomes containing bile salts","volume":"106","author":"KH Song","year":"2005","journal-title":"J Control Release"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.jconrel.2006.06.007","article-title":"Improved intestinal delivery of salmon calcitonin by Lys18-amine specific PEGylation: stability, permeability, pharmacokinetic behavior and in vivo hypocalcemic efficacy","volume":"114","author":"YS Youn","year":"2006","journal-title":"J Control Release"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.actbio.2009.05.032","article-title":"The effect of complexation hydrogels on insulin transport in intestinal epithelial cell models","volume":"6","author":"KM Wood","year":"2010","journal-title":"Acta Biomater"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jconrel.2010.08.007","article-title":"Cyclodextrin complexed insulin encapsulated hydrogel microparticles: An oral delivery system for insulin","volume":"147","author":"S Sajeesh","year":"2010","journal-title":"J Control Release"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ijpharm.2011.04.003","article-title":"Facilitated nanoscale delivery of insulin across intestinal membrane models","volume":"412","author":"CB Woitiski","year":"2011","journal-title":"Int J Pharm"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1208\/s12249-008-9165-2","article-title":"Preparation and characterization of salmon calcitonin-biotin conjugates","volume":"9","author":"M Cetin","year":"2008","journal-title":"AAPS PharmSciTech"},{"key":"ref35","first-page":"e31","article-title":"Regional permeability of salmon calcitonin in isolated rat gastrointestinal tracts: transport mechanism using Caco-2 cell monolayer","volume":"6","author":"RB Shah","year":"2004","journal-title":"AAPS J"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1023\/A:1018819012405","article-title":"Biopharmaceutical approaches for developing and assessing oral peptide delivery strategies and systems: in vitro permeability and in vivo oral absorption of salmon calcitonin (sCT)","volume":"16","author":"PJ Sinko","year":"1999","journal-title":"Pharm Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ejpb.2007.07.009","article-title":"Improved peroral delivery of glucagon-like peptide-1 by site-specific biotin modification: design, preparation, and biological evaluation","volume":"68","author":"YS Youn","year":"2008","journal-title":"Eur J Pharm Biopharm"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1021\/js960067d","article-title":"How structural features influence the biomembrane permeability of peptides","volume":"85","author":"PS Burton","year":"1996","journal-title":"J Pharm Sci"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1023\/A:1015825912542","article-title":"The influence of peptide structure on transport across Caco-2 cells","volume":"8","author":"RA Conradi","year":"1991","journal-title":"Pharm Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1124\/jpet.102.044313","article-title":"Interactions of the dipeptide ester prodrugs of acyclovir with the intestinal oligopeptide transporter: competitive inhibition of glycylsarcosine transport in human intestinal cell line-Caco-2","volume":"304","author":"BS Anand","year":"2003","journal-title":"J Pharmacol Exp Ther"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ijpharm.2005.01.022","article-title":"Current strategies used to enhance the paracellular transport of therapeutic polypeptides across the intestinal epithelium","volume":"294","author":"N Salamat-Miller","year":"2005","journal-title":"Int J Pharm"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/jps.2600840107","article-title":"A biophysical model of passive and polarized active transport processes in Caco-2 cells: approaches to uncoupling apical and basolateral membrane events in the intact cell","volume":"84","author":"NF Ho","year":"1995","journal-title":"J Pharm Sci"},{"key":"ref43","first-page":"1185","article-title":"Transport and uptake characteristics of a new derivative of berberine (CPU-86017) by human intestinal epithelial cell line: Caco-2","volume":"24","author":"HT Yang","year":"2003","journal-title":"Acta Pharmacol Sin"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1006\/excr.1996.0180","article-title":"Regulation of human (Caco-2) intestinal epithelial cell differentiation by extracellular matrix proteins","volume":"225","author":"MD Basson","year":"1996","journal-title":"Exp Cell Res"},{"key":"ref45","first-page":"G71","article-title":"Intestinal peptide YY: ontogeny of gene expression in rat bowel and trophic actions on rat and mouse bowel","volume":"268","author":"G Gomez","year":"1995","journal-title":"Am J Physiol"},{"key":"ref46","first-page":"G312","article-title":"Effect of epidermal growth factor on enterocyte brush-border surface area","volume":"264","author":"JA Hardin","year":"1993","journal-title":"Am J Physiol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"252S","DOI":"10.1042\/bst021252s","article-title":"Membrane peptidase expression by confluent cultures of Caco-2 cells","volume":"21 (Pt3)","author":"IA Brewis","year":"1993","journal-title":"Biochem Soc Trans"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1007\/s11095-007-9488-9","article-title":"Safe and effective permeation enhancers for oral drug delivery","volume":"25","author":"K Whitehead","year":"2008","journal-title":"Pharm Res"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1177\/1087057109352236","article-title":"Feasibility evaluation of 3 automated cellular drug screening assays on a robotic workstation","volume":"15","author":"A Soikkeli","year":"2010","journal-title":"J Biomol Screen"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0057136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T23:39:38Z","timestamp":1595461178000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0057136"}},"subtitle":[],"editor":[{"given":"Jonathan A.","family":"Coles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,2,27]]},"references-count":49,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2013,2,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0057136","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,27]]}}}