{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:45:25Z","timestamp":1785332725217,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,11]],"date-time":"2021-04-11T00:00:00Z","timestamp":1618099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Generalitat de Catalunya Industrial Doctorate program","award":["DI 1989691"],"award-info":[{"award-number":["DI 1989691"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Follicular targeting has gained more attention in recent decades, due to the possibility of obtaining a depot effect in topical administration and its potential as a tool to treat hair follicle-related diseases. Lipid core ethyl cellulose lipomers were developed and optimized, following which characterization of their physicochemical properties was carried out. Dexamethasone was encapsulated in the lipomers (size, 115 nm; polydispersity, 0.24; zeta-potential (Z-potential), +30 mV) and their in vitro release profiles against dexamethasone in solution were investigated by vertical diffusion Franz cells. The skin biodistribution of the fluorescent-loaded lipomers was observed using confocal microscopy, demonstrating the accumulation of both lipomers and fluorochromes in the hair follicles of pig skin. To confirm this fact, immunofluorescence of the dexamethasone-loaded lipomers was carried out in pig hair follicles. The anti-inflammatory (via TNF\u03b1) efficacy of the dexamethasone-loaded lipomers was demonstrated in vitro in an HEK001 human keratinocytes cell culture and the in vitro cytotoxicity of the nanoformulation was investigated.<\/jats:p>","DOI":"10.3390\/pharmaceutics13040533","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T05:52:00Z","timestamp":1618206720000},"page":"533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Dexamethasone-Loaded Lipomers: Development, Characterization, and Skin Biodistribution Studies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-7229","authenticated-orcid":false,"given":"Eloy","family":"Pena-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Topical &amp; Oral Development R+D Reig Jofre Laboratories, 08970 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4080-3516","authenticated-orcid":false,"given":"Maria","family":"Lajarin-Reinares","sequence":"additional","affiliation":[{"name":"Topical &amp; Oral Development R+D Reig Jofre Laboratories, 08970 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5458-3219","authenticated-orcid":false,"given":"Aida","family":"Mata-Ventosa","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology and Experimental Therapeutics, Department of Biochemistry and Molecular Biomedicine, Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain"},{"name":"Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Carlos III Health Institute, 28029 Madrid, Spain"},{"name":"Sant Joan de D\u00e9u Research Institute (IR SJD-CERCA) Esplugues de Llobregat, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2785-5602","authenticated-orcid":false,"given":"Sandra","family":"P\u00e9rez-Torras","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology and Experimental Therapeutics, Department of Biochemistry and Molecular Biomedicine, Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain"},{"name":"Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Carlos III Health Institute, 28029 Madrid, Spain"},{"name":"Sant Joan de D\u00e9u Research Institute (IR SJD-CERCA) Esplugues de Llobregat, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8224-2932","authenticated-orcid":false,"given":"Francisco","family":"Fern\u00e1ndez-Campos","sequence":"additional","affiliation":[{"name":"Topical &amp; Oral Development R+D Reig Jofre Laboratories, 08970 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.0022-202X.2005.23668.x","article-title":"Stratum Corneum Defensive Functions: An Integrated View","volume":"125","author":"Elias","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1517\/17425247.2012.686490","article-title":"Nanocarrier-based topical drug delivery for the treatment of skin diseases","volume":"9","author":"Gupta","year":"2012","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pena-Rodr\u00edguez, E., Moreno, M.C., Blanco-Fernandez, B., Gonz\u00e1lez, J., Fern\u00e1ndez-Campos, F., and Fernandez, B.- (2020). Epidermal Delivery of Retinyl Palmitate Loaded Transfersomes: Penetration and Biodistribution Studies. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020112"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ejpb.2006.10.019","article-title":"Nanoparticles\u2014An efficient carrier for drug delivery into the hair follicles","volume":"66","author":"Lademann","year":"2007","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.2147\/IJN.S132780","article-title":"High drug-loading nanomedicines: Progress, current status, and prospects","volume":"12","author":"Shen","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.colsurfa.2010.12.011","article-title":"Formulation of lipid core nanocapsules","volume":"375","author":"Venturini","year":"2011","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.colsurfa.2013.02.023","article-title":"Polymeric nanocapsules and nanospheres for encapsulation and long sustained release of hydrophobic cyanine-type photosensitizer","volume":"442","author":"Lamch","year":"2014","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1517\/14656566.2011.571209","article-title":"Dexamethasone for ocular inflammation","volume":"12","author":"Saraiya","year":"2011","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejpb.2016.12.005","article-title":"Influence of the skin barrier on the penetration of topical-ly-applied dexamethasone probed by soft X-ray spectromicroscopy","volume":"118","author":"Yamamoto","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1001\/archderm.1972.01620150098034","article-title":"Treatment of alopecia areata with steroid solution","volume":"106","author":"Leyden","year":"1972","journal-title":"Arch Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S42","DOI":"10.1038\/jidsymp.2013.14","article-title":"Current Treatment of Alopecia Areata","volume":"16","author":"Shapiro","year":"2013","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1745-6673-3-26","article-title":"Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity","volume":"3","author":"Lachenmeier","year":"2008","journal-title":"J. Occup. Med. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1016\/j.bbamem.2012.02.013","article-title":"Ethanol perturbs lipid organization in models of stratum corneum membranes: An investigation combining differential scanning calorimetry, infrared and 2H NMR spectroscopy","volume":"1818","author":"Kwak","year":"2012","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1128\/CMR.12.1.147","article-title":"Antiseptics and disinfectants: Activity, action, and resistance","volume":"12","author":"McDonnell","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ejpb.2017.02.001","article-title":"Formulation and ex vivo evaluation of polymeric nanoparticles for controlled delivery of cortico-steroids to the skin and the corneal epithelium","volume":"115","author":"Balzus","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Al-Amin, M.D., Bellato, F., Mastrotto, F., Garofalo, M., Malfanti, A., Salmaso, S., and Caliceti, P. (2020). Dexamethasone Loaded Liposomes by Thin-Film Hydration and Microfluidic Procedures: Formulation Challenges. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051611"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1016\/0378-5173(89)90281-0","article-title":"Nanocapsule formation by interfacial polymer deposition following solvent displacement","volume":"55","author":"Fessi","year":"1989","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lymberopoulos, A., Demopoulou, C., Kyriazi, M., Katsarou, M., Demertzis, N., Hatziandoniou, S., Maswadeh, H., Papaioanou, G., Demetzos, C., and Maibach, H. (2017). Liposome percutaneous penetration in vivo. Toxicol. Res. Appl.","DOI":"10.1177\/2397847317723196"},{"key":"ref_19","unstructured":"(2021, February 10). European Directorate for the Quality of Medicines & HealthCare, European Pharmacopoeia 7.0., Chapter 2.4.24. Identification and Control of Residual Solvents, 01\/2008:20424. Available online: https:\/\/www.drugfuture.com\/Pharmacopoeia\/EP7\/DATA\/20424E.PDF."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1208\/s12248-010-9185-1","article-title":"DDSolver: An Add-In Program for Modeling and Comparison of Drug Dissolution Profiles","volume":"12","author":"Zhang","year":"2010","journal-title":"AAPS J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101852","DOI":"10.1016\/j.jddst.2020.101852","article-title":"In situ bioadhesive film-forming system for topical delivery of mometasone furoate: Characterization and biopharmaceutical properties","volume":"59","author":"Monica","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ijpharm.2005.10.044","article-title":"On the use of the Weibull function for the discernment of drug release mechanisms","volume":"309","author":"Papadopoulou","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.ijbiomac.2018.06.043","article-title":"Magnetic nanocellulose alginate hydrogel beads as potential drug delivery system","volume":"118","author":"Supramaniam","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3109\/03639049509048096","article-title":"Ethylcellulose\u2014A Polymer Review","volume":"21","author":"Rekhi","year":"1995","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0168-3659(94)00096-D","article-title":"Long-acting soluble bioadhesive ophthalmic drug insert (BODI) containing gentamicin for veterinary use: Optimization and clinical investigation","volume":"33","author":"Gurtler","year":"1995","journal-title":"J. Control. Release"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wasilewska, K., and Winnicka, K. (2019). Ethylcellulose\u2014A Pharmaceutical Excipient with Multidirectional Application in Drug Dosage Forms Development. Materials, 12.","DOI":"10.3390\/ma12203386"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.20510\/ukjpb\/6\/i2\/175583","article-title":"Formulation and Evaluation of Besifloxacin Loaded in Situ Gel for Ophthalmic Delivery","volume":"6","author":"Kala","year":"2018","journal-title":"Pharm. Biosci. J."},{"key":"ref_28","unstructured":"(2021, March 18). Committee for Human Medicinal Products, ICH guideline Q3C (R6) on impurities: Guideline for residual solvents 9 August 2019, EMA\/CHMP\/ICH\/82260\/2006. Available online: https:\/\/www.ema.europa.eu\/en\/ich-q3c-r6-residual-solvents."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.ajps.2015.09.004","article-title":"Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: A co-surfactant study","volume":"11","author":"Sharma","year":"2016","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1039\/C5FO01621E","article-title":"Physicochemical, morphological and cellular uptake properties of lutein nanodispersions prepared by using surfactants with different stabilizing mechanisms","volume":"7","author":"Tan","year":"2016","journal-title":"Food Funct."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1166\/jbn.2009.1004","article-title":"Sustained Release from Lipid-Core Nanocapsules by Varying the Core Viscosity and the Particle Surface Area","volume":"5","author":"Venturini","year":"2009","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_32","unstructured":"Singhvi, G., and Singh, M. (2011). Review: In vitro drug release characterization models. Int. J. Pharm. Stud. Res. II, 77\u201384."},{"key":"ref_33","first-page":"314","article-title":"Targeted delivery of a poorly water-soluble compound to hair follicles using polymeric nanoparticle suspensions","volume":"416","author":"Morgen","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jconrel.2016.07.009","article-title":"Ethyl cellulose nanocarriers and nanocrystals differentially deliver dexamethasone into intact, tape-stripped or sodium lauryl sulfate-exposed ex vivo human skin\u2014Assessment by intradermal microdialysis and extraction from the different skin layers","volume":"242","author":"Schumacher","year":"2016","journal-title":"J. Control Release."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/j.0022-202X.2005.23779.x","article-title":"Differential Stripping: Determination of the Amount of Topically Applied Substances Penetrated into the Hair Follicles","volume":"125","author":"Teichmann","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s11095-008-9785-y","article-title":"Dermatopharmacokinetics: Factors Influencing Drug Clearance from the Stratum Corneum","volume":"26","author":"Nicoli","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_37","unstructured":"(2021, March 18). FDA Inactive Ingredient Database, Available online: http:\/\/www.accessdata.fda.gov\/scripts\/cder\/iig\/index.cfm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"494","DOI":"10.4103\/0019-5154.87124","article-title":"Tumor necrosis factor-alpha in patients with alopecia areata","volume":"56","author":"Prohic","year":"2011","journal-title":"Indian J. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.jaad.2014.03.005","article-title":"Alopecia areata occurring during anti-TNF therapy: A national multicenter prospective study","volume":"70","author":"Tauber","year":"2014","journal-title":"J. Am. Acad. Dermatol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/4\/533\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:12:19Z","timestamp":1760364739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/4\/533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,11]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["pharmaceutics13040533"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13040533","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,11]]}}}