{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:17:19Z","timestamp":1761718639219,"version":"build-2065373602"},"reference-count":74,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T00:00:00Z","timestamp":1511222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Halobetasol propionate (HB) is a potent synthetic corticosteroid used against inflammatory skin diseases, such as dermatitis, eczema, and psoriasis, among others. The aim of this study is to define how the presence of different skin penetration enhancers (nonane, menthone, limonene, azone, carene, decanol, linoleic acid and cetiol) affects the penetration and retention in skin of HB. To determine drug penetration through skin, 5% of each promoter was used in an ex vivo system with human skin on Franz cells. The results showed that the highest permeation occurs in the presence of menthone, followed by nonane. Permeation parameters were determined. The in vivo test was assessed, and the formulation containing HB-menthone presented better anti-inflammatory efficacy. These results are useful to generate a specific treatment according to each patient\u2019s needs, and the inflammatory characteristics of the disease.<\/jats:p>","DOI":"10.3390\/ijms18112475","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T11:23:20Z","timestamp":1511263400000},"page":"2475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effect of Different Skin Penetration Promoters in Halobetasol Propionate Permeation and Retention in Human Skin"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2924-3124","authenticated-orcid":false,"given":"Paulina","family":"Carvajal-Vidal","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9316-8459","authenticated-orcid":false,"given":"Mireia","family":"Mallandrich","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-4821","authenticated-orcid":false,"given":"Ana","family":"Calpena","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000056393","article-title":"Modulation of the barrier function of the skin","volume":"14","author":"Hadgraft","year":"2001","journal-title":"Skin Pharmacol. Appl. Skin Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0163-7827(02)00028-0","article-title":"Structure of the skin barrier and its modulation by vesicular formulations","volume":"42","author":"Bouwstra","year":"2003","journal-title":"Prog. Lipid Res."},{"key":"ref_3","first-page":"1","article-title":"The structure and function of skin","volume":"Volume 119","author":"Walters","year":"2002","journal-title":"Dermatological and Transdermal Formulations"},{"key":"ref_4","unstructured":"Hsieh, D. (1993). Drug Permeation Enhancement: Theory and Applications, CRC Press. [1st ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1111\/j.1365-2125.2007.03065.x","article-title":"The role of hair follicles in the percutaneous absorption of caffeine","volume":"1","author":"Otberg","year":"2008","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1087-0024.2005.10121.x","article-title":"Follicular penetration and targeting","volume":"1","author":"Lademann","year":"2005","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1056\/NEJM199503023320907","article-title":"Treatment of psoriasis","volume":"2","author":"Greaves","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"306","article-title":"Effectiveness of topical therapy for psoriasis: Results of a national survey","volume":"55","author":"Liem","year":"1995","journal-title":"Cutis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/0190-9622(91)70312-P","article-title":"Dermatopharmacologic investigations of halobetasol propionate in comparison with clobetasol 17-propionate","volume":"25","author":"Yawalkar","year":"1991","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_10","first-page":"41","article-title":"Common skin disorder and Their Topical Treatment","volume":"Volume 119","author":"Long","year":"2002","journal-title":"Dermatological and Transdermal Formulations"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/0190-9622(91)70315-S","article-title":"A comparative, multicenter, double blind trial of 0.05% halobetasol propionate ointment and 0.1% betamethasone valerate ointment in the treatment of patients with chronic, localized plaque psoriasis","volume":"25","author":"Blum","year":"1991","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/0190-9622(91)70319-W","article-title":"Halobetasol propionate cream by day and halobetasol propionate ointment at night for the treatment of pediatric patients with chronic, localized plaque psoriasis and atopic dermatitis","volume":"25","author":"Herz","year":"1991","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.bbamem.2004.01.006","article-title":"Hydrocortisone and dexamethasone in very deformable drug carriers have increased biological potency, prolonged effect, and reduced therapeutic dosage","volume":"1663","author":"Cevc","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1365-4362.1990.tb02567.x","article-title":"Treatment of localized vitiligo with Ulobetasol cream","volume":"29","author":"Xunquan","year":"1990","journal-title":"Int. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1468-3083.2009.03358.x","article-title":"Topical corticosteroids in psoriasis: Strategies for improving safety","volume":"24","author":"Horn","year":"2010","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_16","unstructured":"Maibach, H.I., and Surber, C. (1992). Halobetasol propionate. Topical Corticosteroids, Karger."},{"key":"ref_17","unstructured":"(2017, September 21). Food and Drug Administration, Available online: https:\/\/www.fda.gov\/."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/0002-9378(90)90394-M","article-title":"Severe symmetric intrauterine growth retardation associated with the topical use of triamcinolone","volume":"162","author":"Katz","year":"1990","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/0190-9622(91)70313-Q","article-title":"A double-blind, multicenter comparison of 0.05% halobetasol propionate ointment and 0.05% clobetasol propionate ointment in patients with chronic, localized plaque psoriasis","volume":"25","author":"Goldberg","year":"1992","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_20","unstructured":"Vademecum (2017, August 24). Halobetasol Propionate. Available online: http:\/\/www.iqb.es\/cbasicas\/farma\/farma04\/h014.htm."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Banga, A.K. (2011). Transdermal and Intradermal Delivery of Therapeutic Agents: Application of Physical Technologies, CRC Press. [1st ed.].","DOI":"10.1201\/b10906"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Banga, A.K. (1998). Electrically Assisted Transdermal and Topical Drug Delivery, CRC Press. [1st ed.].","DOI":"10.4324\/9780203483985"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1517\/17425240902841935","article-title":"Microporation applications for enhancing drug delivery","volume":"6","author":"Banga","year":"2009","journal-title":"Exp. Opin. Drug Deliv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.addr.2012.09.032","article-title":"Penetration enhancers","volume":"64","author":"Williams","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ejpb.2015.01.025","article-title":"Dual-directional regulation of drug permeating amount by combining the technique of ion-pair complexation with chemical enhancers for the synchronous permeation of indapamide and bisoprolol in their compound patch through rabbit skin","volume":"91","author":"Song","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1046\/j.1365-4362.2001.01161.x","article-title":"Azone\u00ae enhances clinical effectiveness of an optimized formulation of triamcinolone acetonide in atopic dermatitis","volume":"40","author":"Cato","year":"2001","journal-title":"Int. J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S1461-5347(99)00225-4","article-title":"Percutaneous penetration enhancers: Local versus transdermal activity","volume":"3","author":"Asbill","year":"2000","journal-title":"Pharm. Sci. Technol. Today"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"593","DOI":"10.2174\/0929867003374840","article-title":"Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery","volume":"7","author":"Kanikkannan","year":"2000","journal-title":"Curr. Med. Chem."},{"key":"ref_29","first-page":"3","article-title":"Dermatological formulations: Percutaneous absorption","volume":"73","author":"Maibach","year":"1984","journal-title":"J. Pharm. Sci."},{"key":"ref_30","unstructured":"(2017, October 02). Badische Anilin- und Soda-Fabrik (BASF). Available online: https:\/\/www.ulprospector.com\/es\/eu\/PersonalCare\/Detail\/804\/31779\/Cetiol-CC."},{"key":"ref_31","first-page":"313","article-title":"Effect of limonene and related compounds on the percutaneous absorption of indomethacin","volume":"4","author":"Okabe","year":"1989","journal-title":"Drug Des. Deliv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/jps.22271","article-title":"Potential use of nanostructured lipid carriers for topical delivery of flurbiprofen","volume":"100","author":"Egea","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/j.1439-0507.2012.02202.x","article-title":"Evaluation of novel nystatin nanoemulsion for skin candidosis infections","volume":"56","author":"Clares","year":"2013","journal-title":"Mycoses"},{"key":"ref_34","unstructured":"(2017, September 15). Scientific Committee on Consumer Safety 2017. Available online: https:\/\/ec.europa.eu\/health\/sites\/health\/files\/scientific_committees\/consumer_safety\/docs\/sccs_o_206.pdf."},{"key":"ref_35","unstructured":"(2017, August 02). Organization for Economic Co-Operation and Development (OECD), Guidelines for the Testing of Chemicals, Section 4 Test No. 404: Acute Dermal Irritation\/Corrosion. Available online: http:\/\/www.oecd.org\/env\/test-no-404-acute-dermal-irritation-corrosion-9789264242678-en.htm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1002\/aic.690210522","article-title":"Drug permeation through human skin: Theory and in-vitro experimental measurement","volume":"21","author":"Michaels","year":"1975","journal-title":"AIChE J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0378-5173(92)90032-W","article-title":"On the non-Gaussian distribution of human skin permeabilities","volume":"86","author":"Williams","year":"1992","journal-title":"Int. J. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0022-3565(25)08751-8","article-title":"Methods for the Study of irritation and toxicity of substances applied topically to the skin and mucous membranes","volume":"82","author":"Draize","year":"1944","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"329","DOI":"10.4103\/0019-5154.74531","article-title":"Study of reservoir effect of clobetasol propionate cream in an experimental animal model using histamine-induced wheal suppression test","volume":"55","author":"Abidi","year":"2010","journal-title":"Indian J. Dermatol."},{"key":"ref_40","unstructured":"United States Pharmacopeia Convention Inc. (2017). The United States Pharmacopeia, the National Formulary, USP40\/NF35, National Publishing for the United States Pharmacopeial Convention, Inc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0731-7085(01)00581-7","article-title":"Spectrophotometric determination of clobetasol propionate, halobetasol propionate, quinagolide hydrochloride, through charge transfer complexation","volume":"27","author":"Mostafa","year":"2002","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_42","first-page":"103","article-title":"Formulation and evaluation of novel combined halobetasol propionate and fusidic acid ointment","volume":"1","author":"Chakole","year":"2009","journal-title":"Int. J. Chem. Tech. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/chromsci\/bmu029","article-title":"Quantification of halobetasol propionate and its impurities present in topical dosage forms by stability-indicating LC method","volume":"53","author":"Nalwade","year":"2015","journal-title":"J. Chromatogr. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10800-011-0368-y","article-title":"Carbon nanotube-based electrochemical sensor for the determination of halobetasol propionate, a topical corticosteroid","volume":"42","author":"Goyal","year":"2012","journal-title":"J. Appl. Electrochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1093\/chromsci\/bmu027","article-title":"Impurity profiling and a stability-indicating UPLC method development and validation for the estimation of related impurities of halobetasol propionate in halobetasol propionate 0.05% (w\/w) cream","volume":"53","author":"Prakash","year":"2015","journal-title":"J. Chromatogr. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3109\/08982104.2013.843192","article-title":"Halobetasol propionate-loaded solid lipid nanoparticles (SLN) for skin targeting by topical delivery","volume":"24","author":"Bikkad","year":"2014","journal-title":"J. Liposome Res."},{"key":"ref_47","unstructured":"(2017, September 08). Gattefoss\u00e9. Available online: https:\/\/www.gattefosse.com\/transcutol-p."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0022-2275(20)38006-8","article-title":"Human epidermal lipids: Characterization and modulations during differentiation","volume":"24","author":"Lampe","year":"1983","journal-title":"J. Lipid Res."},{"key":"ref_49","unstructured":"Swarbrick, J., and Boylan, J.C. (1995). Encyclopedia of Pharmaceutical Technology: Preservation of Pharmaceutical Products to Salt Forms of Drugs and Absorption, CRC Press."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0378-5173(94)00143-X","article-title":"Effects of some non-toxic penetration enhancers on in vitro heparin skin permeation from gel vehicles","volume":"111","author":"Bonina","year":"1994","journal-title":"Int. J. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1001\/archderm.1982.01650190028013","article-title":"Enhanced percutaneous penetration with 1-dodecylazacycloheptan-2-one","volume":"118","author":"Stoughton","year":"1982","journal-title":"Arch. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1002\/jps.2600731234","article-title":"Concentration-dependent enhancement of 1dodecylazacycloheptan-2-one on the percutaneous penetration kinetics of triamcinolone acetonide","volume":"73","author":"Chow","year":"1984","journal-title":"J. Pharm. Sci."},{"key":"ref_53","unstructured":"Smith, E.W., and Maibach, H.I. (1995). Percutaneous Penetration Enhancers, CRC Press. [1st ed.]."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0378-5173(93)90287-P","article-title":"Nonane enhances propranolol hydrochloride penetration in human skin","volume":"92","author":"Melendres","year":"1993","journal-title":"Int. J. Pharm."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/jps.2600800109","article-title":"Enhancement of propranolol hydrochloride and diazepam skin absorption in vitro: Effect of enhancer lipophilicity","volume":"80","author":"Hori","year":"1991","journal-title":"J. Pharm. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1023\/A:1015921702258","article-title":"Structure\/Effect studies of fatty acid isomers as skin penetration enhancers and skin irritants","volume":"6","author":"Aungst","year":"1989","journal-title":"Pharm. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.2042-7158.1985.tb05070.x","article-title":"Optimization of bioavailability of topical steroids: Non-occluded penetration enhancers under thermodynamic control","volume":"37","author":"Bennett","year":"1985","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0378-5173(98)00088-X","article-title":"Influence of penetration enhancers on the blanching intensity of betamethasone 17-benzoate","volume":"168","author":"Bach","year":"1998","journal-title":"Int. J. Pharm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.2042-7158.1987.tb03173.x","article-title":"Effect of penetration enhancers on the permeation of mannitol, hydrocortisone and progesterone through human skin","volume":"39","author":"Barry","year":"1987","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_60","first-page":"259","article-title":"d-Limonene: Safety and clinical applications","volume":"12","author":"Sun","year":"2007","journal-title":"Altern. Med. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Dragicevic, N., and Maibach, H.I. (2016). Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Nanocarriers, Springer.","DOI":"10.1007\/978-3-662-47862-2"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Chang, J., and Gupta, G. (2010). Tissue Engineering for the Hand: Research Advances and Clinical Applications, World Scientific.","DOI":"10.1142\/9789814313568"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1046\/j.1524-475x.2001.00066.x","article-title":"The pig as a model for human wound healing","volume":"9","author":"Sullivan","year":"2001","journal-title":"Wound Repair Regen."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/01.BCR.0000169885.66639.B5","article-title":"Models of Wound Healing","volume":"26","author":"Greenhalgh","year":"2005","journal-title":"J. Burn Care Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1001\/archderm.1963.01590190026002","article-title":"Existence of reservoir in the stratum corneum: Experimental proof","volume":"88","author":"Vickers","year":"1963","journal-title":"Arch. Dermatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1159\/000401278","article-title":"Quantitative determination of percutaneous absorption of radiolabeled drugs in vitro and in vivo by human skin","volume":"7","author":"Schaefer","year":"1978","journal-title":"Curr. Probl. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1046\/j.1365-2133.1999.02859.x","article-title":"Effect of barrier perturbation on cutaneous salicylic acid penetration in human skin: In vivo pharmacokinetics using micro dialysis and non-invasive quantification of barrier function","volume":"140","author":"Benfeldt","year":"1999","journal-title":"Br. J. Dermatol."},{"key":"ref_68","unstructured":"(2017, August 25). International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. Validation of Analytical Procedures: Text and Methodology. Q2 (R1). Available online: https:\/\/www.ich.org\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/Quality\/Q2_R1\/Step4\/Q2_R1__Guideline.pdf."},{"key":"ref_69","unstructured":"Pubchem (2017, August 26). Open Chemistry Database, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Halobetasol#section=Top."},{"key":"ref_70","unstructured":"ECVAM (2017, August 20). Test Guideline for Skin Absorption: In Vitro Method. Official Journal of the European Union Method B.45 of Annex to 440\/2008\/EC (EU Test Methods Regulation) and Its Corrigendum. Available online: http:\/\/www.iss.it\/binary\/hclp\/cont\/Reg._440_2008.pdf."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/1523-1747.ep12533356","article-title":"Percutaneous Absorption: On the Relevance of in Vitro Data","volume":"64","author":"Franz","year":"1975","journal-title":"J. Investig. Dermatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1007\/s11095-017-2181-8","article-title":"Developing transdermal applications of ketorolac tromethamine entrapped in stimuli sensitive block copolymer hydrogels","volume":"34","author":"Mallandrich","year":"2017","journal-title":"Pharm. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1002\/jps.23249","article-title":"Development and characterization of a novel nystatin-loaded nanoemulsion for the buccal treatment of candidiasis: Ultrastructural effects and release studies","volume":"101","author":"Campos","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Passantino, A. (2008). Application of the 3Rs principles for animals used for experiments at the beginning of the 21st century. Ann. Rev. Biomed. Sci., 10.","DOI":"10.5016\/1806-8774.2008.v10pT27"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/11\/2475\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:50:33Z","timestamp":1760208633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/11\/2475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,21]]},"references-count":74,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2017,11]]}},"alternative-id":["ijms18112475"],"URL":"https:\/\/doi.org\/10.3390\/ijms18112475","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2017,11,21]]}}}