{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:19:38Z","timestamp":1789841978464,"version":"4.0.1"},"reference-count":50,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["407985\/2013-1"],"award-info":[{"award-number":["407985\/2013-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["407985\/2013-1"],"award-info":[{"award-number":["407985\/2013-1"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Goi\u00e1s","award":["407985\/2013-1"],"award-info":[{"award-number":["407985\/2013-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Tr\u00e9cul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-\u03b2-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-\u03b2-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc &lt; 500 M\u22121). PSO and 5-MOP permeability rate decreased after adding HP-\u03b2-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-\u03b2-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-\u03b2-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.<\/jats:p>","DOI":"10.3390\/molecules27144580","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T05:37:53Z","timestamp":1658209073000},"page":"4580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Improvement in Solubility\u2013Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-\u03b2-cyclodextrin"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1811-8408","authenticated-orcid":false,"given":"R\u00fabia Darc","family":"Machado","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Biofarm\u00e1cia e Farmacocin\u00e9tica (BioPk), Faculdade de Farm\u00e1cia, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74605-170, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00falio C. G.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biofarm\u00e1cia e Farmacocin\u00e9tica (BioPk), Faculdade de Farm\u00e1cia, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74605-170, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-237X","authenticated-orcid":false,"given":"Lu\u00eds A. D.","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Nanotecnologia Farmac\u00eautica e Sistemas de Libera\u00e7\u00e3o de F\u00e1rmacos (FarmaTec), Faculdade de Farm\u00e1cia, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74605-170, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7936-5429","authenticated-orcid":false,"given":"Gerlon de A. R.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Resson\u00e2ncia Magn\u00e9tica Nuclear (LabRMN), Instituto de Qu\u00edmica, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74605-170, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9985-2980","authenticated-orcid":false,"given":"Luciano M.","family":"Li\u00e3o","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Resson\u00e2ncia Magn\u00e9tica Nuclear (LabRMN), Instituto de Qu\u00edmica, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74605-170, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-5803","authenticated-orcid":false,"given":"Eliana M.","family":"Lima","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Nanotecnologia Farmac\u00eautica e Sistemas de Libera\u00e7\u00e3o de F\u00e1rmacos (FarmaTec), Faculdade de Farm\u00e1cia, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74605-170, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3497-4885","authenticated-orcid":false,"given":"Mariana C.","family":"de Morais","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de PD&I de Bioprodutos, Faculdade de Farm\u00e1cia, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74605-170, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edemilson C.","family":"da Concei\u00e7\u00e3o","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de PD&I de Bioprodutos, Faculdade de Farm\u00e1cia, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74605-170, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3813-8545","authenticated-orcid":false,"given":"K\u00eannia R.","family":"Rezende","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biofarm\u00e1cia e Farmacocin\u00e9tica (BioPk), Faculdade de Farm\u00e1cia, Universidade Federal de Goi\u00e1s, Goi\u00e2nia 74605-170, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1600-0781.2011.00606.x","article-title":"Photo(Chemo)Therapy for Vitiligo","volume":"27","author":"Pacifico","year":"2011","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"113593","DOI":"10.1016\/j.jpba.2020.113593","article-title":"Crude Plant Extract versus Single Compounds for Vitiligo Treatment: Ex Vivo Intestinal Permeability Assessment on Brosimum gaudichaudii Tr\u00e9cul","volume":"191","author":"Machado","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1021\/np50093a015","article-title":"Coumarins from Brosimum gaudichaudii","volume":"56","author":"Vilegas","year":"1993","journal-title":"J. Nat. Prod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1590\/S0103-50532002000200023","article-title":"Prenylated Coumarins, Chalcone and New Cinnamic Acid and Dihydrocinnamic Acid Derivatives from Brosimum gaudichaudii","volume":"13","author":"Mathias","year":"2002","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1590\/S0102-33062007000300006","article-title":"Morfoanatomia e Histoqu\u00edmica de Brosimum gaudichaudii Tr\u00e9cul (Moraceae)","volume":"21","author":"Jacomassi","year":"2007","journal-title":"Acta Bot. Bras."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1556\/ABot.48.2006.1-2.12","article-title":"Morphology of Stem and Subterranean System of Brosimum gaudichaudii (Moraceae)","volume":"48","author":"Palhares","year":"2006","journal-title":"Acta Bot. Hung."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jep.2017.04.023","article-title":"Ethnobotanical Study of Medicinal Plants Used by Ribeirinhos in the North Araguaia Microregion, Mato Grosso, Brazil","volume":"205","author":"Ribeiro","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111685","DOI":"10.1016\/j.molliq.2019.111685","article-title":"Microemulsions Incorporating Brosimum gaudichaudii Extracts as a Topical Treatment for Vitiligo: In Vitro Stimulation of Melanocyte Migration and Pigmentation","volume":"294","author":"Borin","year":"2019","journal-title":"J. Mol. Liq."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s12272-010-0206-5","article-title":"Pharmacokinetics, Tissue Distribution and Excretion of Coumarin Components from Psoralea corylifolia L. in Rats","volume":"33","author":"Feng","year":"2010","journal-title":"Arch. Pharm. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1159\/000029835","article-title":"Drug Monitoring of Orally Administered 8-Methoxypsoralen in Patients Treated with Extracorporeal Photopheresis","volume":"11","author":"Balogh","year":"1998","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jchromb.2003.09.051","article-title":"Determination of 8-Methoxypsoralen in Human Plasma, and Microdialysates Using Liquid Chromatography\u2013Tandem Mass Spectrometry","volume":"798","author":"Seegel","year":"2003","journal-title":"J. Chromatogr. B"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1600-0781.1998.tb00029.x","article-title":"Plasma Levels of 8-Methoxypsoralen Following PUVA-Bath Photochemotherapy","volume":"14","author":"Kobyletzki","year":"1998","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/j.1600-0781.1999.tb00059.x","article-title":"Pharmacokinetics of 8-Methoxypsoralen during Extracorporeal Photopheresis","volume":"15","author":"Shephard","year":"1999","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1365-2133.1991.tb06040.x","article-title":"Plasma Levels of 8-Methoxypsoralen Following Oral or Bath-Water Treatment","volume":"125","author":"Thomas","year":"1991","journal-title":"Br. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1016\/j.biopha.2017.01.157","article-title":"Complexation of Phytochemicals with Cyclodextrin Derivatives\u2014An Insight","volume":"88","author":"Suvarna","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105882","DOI":"10.1016\/j.foodhyd.2020.105882","article-title":"Latest Developments in the Application of Cyclodextrin Host-Guest Complexes in Beverage Technology Processes","volume":"106","author":"Astray","year":"2020","journal-title":"Food Hydrocoll."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jpba.2015.01.058","article-title":"Analytical Techniques for Characterization of Cyclodextrin Complexes in the Solid State: A Review","volume":"113","author":"Mura","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"132467","DOI":"10.1016\/j.foodchem.2022.132467","article-title":"Cyclodextrins Inclusion Complex: Preparation Methods, Analytical Techniques and Food Industry Applications","volume":"384","author":"Rakmai","year":"2022","journal-title":"Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1080\/10610270410001713321","article-title":"X-Ray Structure and Thermal Properties of a 1:1 Inclusion Complex Between Permethylated \u03b2-Cyclodextrin and Psoralen","volume":"16","author":"Caira","year":"2004","journal-title":"Supramol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4103\/2230-973X.121284","article-title":"Cavamax W7 Composite Psoralen Ethosomal Gel versus Cavamax W7 Psoralen Solid Complex Gel for Topical Delivery: A Comparative Evaluation","volume":"3","author":"Pathak","year":"2013","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_21","first-page":"543","article-title":"Improvement of Dissolution Characteristics of Psoralen by Cyclodextrins Complexation","volume":"50","author":"Vincieri","year":"1995","journal-title":"Farmaco"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2165\/00137696-200402040-00006","article-title":"Role of Cyclodextrins in Improving Oral Drug Delivery","volume":"2","author":"Loftsson","year":"2004","journal-title":"Am. J. Drug Deliv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ijpharm.2017.11.018","article-title":"Cyclodextrins: Structure, Physicochemical Properties and Pharmaceutical Applications","volume":"535","author":"Jansook","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ejps.2010.04.014","article-title":"Evaluation of the Cytotoxicity of \u03b2-Cyclodextrin Derivatives: Evidence for the Role of Cholesterol Extraction","volume":"40","author":"Kiss","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.drudis.2015.11.016","article-title":"Cyclodextrins in Pharmaceutical Formulations II: Solubilization, Binding Constant, and Complexation Efficiency","volume":"21","author":"Jambhekar","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ijpharm.2007.04.029","article-title":"Effect of the Unstirred Water Layer on Permeability Enhancement by Hydrophilic Cyclodextrins","volume":"342","author":"Brewster","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1517\/17425247.2.1.335","article-title":"Cyclodextrins in Drug Delivery","volume":"2","author":"Loftsson","year":"2005","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1002\/jps.22033","article-title":"The Solubility-Permeability Interplay in Using Cyclodextrins as Pharmaceutical Solubilizers: Mechanistic Modeling and Application to Progesterone","volume":"99","author":"Dahan","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_29","first-page":"531","article-title":"Literature Review of Cyclodextrins Inclusion Complexes Characterization\u2014Part I: Phase Solubility Diagram, Dissolution and Scanning Electron Microscopy","volume":"12","author":"Takahashi","year":"2012","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s10847-010-9756-x","article-title":"Drug\/Cyclodextrin: Beyond Inclusion Complexation","volume":"69","author":"Kurkov","year":"2011","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ijpharm.2005.05.042","article-title":"Evaluation of Cyclodextrin Solubilization of Drugs","volume":"302","author":"Loftsson","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/jps.21861","article-title":"Cyclodextrins as Solubilizers: Formation of Complex Aggregates","volume":"99","author":"Jansook","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.indcrop.2018.12.045","article-title":"\u03b2-Cyclodextrin Complexation of Extracts of Olive Leaves Obtained by Pressurized Liquid Extraction","volume":"129","author":"Jaski","year":"2019","journal-title":"Ind. Crop. Prod."},{"key":"ref_34","first-page":"16","article-title":"A Literature Review of Cyclodextrin Inclusion Complexes Characterization\u2014Part III: Differential Scanning Calorimetry and Thermogravimetry","volume":"12","author":"Takahashi","year":"2012","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0040-6031(01)00665-7","article-title":"Thermal Analysis of Cyclodextrins and Their Inclusion Compounds","volume":"380","author":"Giordano","year":"2001","journal-title":"Thermochim. Acta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1208\/s12249-022-02218-8","article-title":"Formulation of Apigenin-Cyclodextrin-Chitosan Ternary Complex: Physicochemical Characterization, In Vitro and In Vivo Studies","volume":"23","author":"Jafar","year":"2022","journal-title":"AAPS PharmSciTech"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ejps.2015.08.001","article-title":"Influence of Hydrophilic Polymers on the Complexation of Carbamazepine with Hydroxypropyl-\u03b2-Cyclodextrin","volume":"78","author":"Kachrimanis","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zafar, A., Alruwaili, N.K., Imam, S.S., Alsaidan, O.A., Alkholifi, F.K., Alharbi, K.S., Mostafa, E.M., Alanazi, A.S., Gilani, S.J., and Musa, A. (2021). Formulation of Genistein-HP \u03b2 Cyclodextrin-Poloxamer 188 Ternary Inclusion Complex: Solubility to Cytotoxicity Assessment. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13121997"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1002\/jps.24372","article-title":"A Sensitive Medium-Throughput Method to Predict Intestinal Absorption in Humans Using Rat Intestinal Tissue Segments","volume":"104","author":"Antunes","year":"2015","journal-title":"J. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2006.10.044","article-title":"Cyclodextrins and Their Pharmaceutical Applications","volume":"329","author":"Loftsson","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ijpharm.2019.02.004","article-title":"Self-Association of Cyclodextrins and Cyclodextrin Complexes in Aqueous Solutions","volume":"560","author":"Loftsson","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1007\/s13346-019-00691-6","article-title":"Antiviral Effect of Phytochemicals from Medicinal Plants: Applications and Drug Delivery Strategies","volume":"10","author":"Yarmolinsky","year":"2020","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1208\/s12249-021-01936-9","article-title":"Orally Administered Drug Solubility-Enhancing Formulations: Lesson Learnt from Optimum Solubility-Permeability Balance","volume":"22","author":"Pawar","year":"2021","journal-title":"AAPS PharmSciTech"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ijpharm.2017.10.058","article-title":"Active Intestinal Drug Absorption and the Solubility-Permeability Interplay","volume":"537","author":"Porat","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1021\/acs.molpharmaceut.9b00057","article-title":"Methacrylate-Copolymer Eudragit EPO as a Solubility-Enabling Excipient for Anionic Drugs: Investigation of Drug Solubility, Intestinal Permeability, and Their Interplay","volume":"16","author":"Dahan","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.bjp.2017.12.002","article-title":"Validation of a Photostability Indicating Method for Quantification of Furanocoumarins from Brosimum gaudichaudii Soft Extract","volume":"28","author":"Ferreira","year":"2018","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_47","first-page":"117","article-title":"Phase Solubility Techniques","volume":"4","author":"Higuchi","year":"1965","journal-title":"Adv. Anal. Chem. Instrum."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.1021\/ja00119a048","article-title":"Excitation Sculpting in High-Resolution Nuclear Magnetic Resonance Spectroscopy: Application to Selective NOE Experiments","volume":"117","author":"Stott","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1385\/1-59259-185-X:233","article-title":"Applications of Epithelial Cell Culture in Studies of Drug Transport","volume":"Volume 188","author":"Tavelin","year":"2002","journal-title":"Epithelial Cell Culture Protocols"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.vascn.2014.11.004","article-title":"Variability of Permeability Estimation from Different Protocols of Subculture and Transport Experiments in Cell Monolayers","volume":"71","author":"Casabo","year":"2015","journal-title":"J. Pharmacol. Toxicol. Methods"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/14\/4580\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:53:26Z","timestamp":1760140406000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/14\/4580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,19]]},"references-count":50,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["molecules27144580"],"URL":"https:\/\/doi.org\/10.3390\/molecules27144580","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,19]]}}}