{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T23:02:12Z","timestamp":1769727732253,"version":"3.49.0"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid\u2019s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications.<\/jats:p>","DOI":"10.3390\/pharmaceutics17070867","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T06:46:12Z","timestamp":1751438772000},"page":"867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Topical Percutaneous Drug Delivery for Allergic Diseases: A Novel Strategy for Site-Directed Pharmacologic Modulation"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3037-8082","authenticated-orcid":false,"given":"Mitsuhiro","family":"Kamimura","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, National Hospital Organization Disaster Medical Center, Tokyo 190-0014, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0091-4366","authenticated-orcid":false,"given":"Hiroaki","family":"Todo","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1332-2001","authenticated-orcid":false,"given":"Kenji","family":"Sugibayashi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama 350-0295, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9044-3061","authenticated-orcid":false,"given":"Koichiro","family":"Asano","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0140-6736(06)69283-0","article-title":"Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys","volume":"368","author":"Asher","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/S0140-6736(11)60130-X","article-title":"Allergic rhinitis","volume":"378","author":"Greiner","year":"2011","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41572-020-00227-0","article-title":"Allergic rhinitis","volume":"6","author":"Bousquet","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.alit.2022.07.005","article-title":"Executive summary: Japanese guidelines for allergic conjunctival diseases 2021","volume":"71","author":"Miyazaki","year":"2022","journal-title":"Allergol. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"273","DOI":"10.2500\/ajra.2015.29.4215","article-title":"Intranasal spray medications for maintenance therapy of allergic rhinitis","volume":"29","author":"Berger","year":"2015","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1097\/ACI.0b013e328364ec3a","article-title":"Allergic conjunctivitis: An update on diagnosis and management","volume":"13","year":"2013","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_7","unstructured":"Global Initiative for Asthma (GINA) (2024). Global Strategy for Asthma Management and Prevention, 2024 Update, GINA. Available online: https:\/\/ginasthma.org."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"44","DOI":"10.53986\/ibjm.2021.0008","article-title":"Application of diphenydramine 0ointment to the eyelids for allergic conjunctivitis","volume":"3","author":"Kamimura","year":"2021","journal-title":"Iberoam. J. Med."},{"key":"ref_9","first-page":"170","article-title":"A Pilot Study of Transdermal Application of Diphenhydramine to the Nasal Ala in Patients with Allergic Rhinitis and Asthma","volume":"47","author":"Kamimura","year":"2022","journal-title":"Tokai J. Exp. Clin. Med."},{"key":"ref_10","first-page":"152","article-title":"Transdermal Application of Steroid to Cervical Trachea for the Cough in Patients with Bronchial Asthma and Cough Variant Asthma-A Pilot Study","volume":"4","author":"Kamimura","year":"2013","journal-title":"J. Allergy Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s10384-024-01108-9","article-title":"Safety and efficacy of a novel 0.5% epinastine topical eyelid cream in allergic conjunctivitis: A phase 3 trial","volume":"68","author":"Fujishima","year":"2024","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/nbt.1504","article-title":"Transdermal drug delivery","volume":"26","author":"Prausnitz","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1248\/bpb.30.2135","article-title":"Analysis of skin disposition of flurbiprofen after topical application using dual agar gel discs-inserted rats","volume":"30","author":"Hasegawa","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s00167-013-2408-0","article-title":"Penetration of topical diclofenac sodium 4% spray gel into the synovial tissue and synovial fluid of the knee: A randomised clinical trial","volume":"22","author":"Efe","year":"2014","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1759720X20943088","DOI":"10.1177\/1759720X20943088","article-title":"Penetration of topical diclofenac into synovial tissue and fluid of osteoarthritic knees: A multicenter, randomized, placebo-controlled, pharmacokinetic study","volume":"12","author":"Seefried","year":"2020","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/S0022-3565(25)38459-4","article-title":"Skin permeability and local tissue concentrations of nonsteroidal anti-inflammatory drugs after topical application","volume":"268","author":"Singh","year":"1994","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1111\/j.2042-7158.1994.tb03250.x","article-title":"Deep tissue penetration of bases and steroids after dermal application in rat","volume":"46","author":"Singh","year":"1994","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13075-018-1619-7","article-title":"H1-antihistamines are associated with lower prevalence of radiographic knee osteoarthritis: A cross-sectional analysis of the Osteoarthritis Initiative data","volume":"20","author":"Shirinsky","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1017\/S026502150600202X","article-title":"Comparison of diphenhydramine and lidocaine for prevention of pain after injection of propofol: A double-blind, placebo-controlled, randomized study","volume":"24","author":"Apiliogullari","year":"2007","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000354151","article-title":"Prompt analgesic effect of antihistaminic diphenhydramine ointment on bone-joint-muscle pain as assessed by skin impedance","volume":"92","author":"Fujita","year":"2013","journal-title":"Pharmacology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1001\/archopthalmol.2011.1788","article-title":"Influence of parental health literacy and dosing responsibility on pediatric glaucoma medication adherence","volume":"130","author":"Freedman","year":"2012","journal-title":"Arch. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Uchino, M., Yokoi, N., Shimazaki, J., Hori, Y., Tsubota, K., and on behalf of the Japan Dry Eye Society (2022). Adherence to Eye Drops Usage in Dry Eye Patients and Reasons for Non-Compliance: A Web-Based Survey. J. Clin. Med., 11.","DOI":"10.3390\/jcm11020367"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1080\/01676830.2020.1812094","article-title":"Ultrasound biomicroscopic features of the normal lower eyelid","volume":"40","author":"Vasanthapuram","year":"2021","journal-title":"Orbit"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1136\/bjo.83.7.767","article-title":"New treatment of dry eye: The effect of calcium ointment through eyelid skin delivery","volume":"83","author":"Tsubota","year":"1999","journal-title":"Br. J. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ijpharm.2017.09.070","article-title":"Eyelid skin as a potential site for drug delivery to conjunctiva and ocular tissues","volume":"533","author":"See","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1248\/cpb.55.1002","article-title":"Development of a stick-type transdermal eyelid delivery system of ketotifen fumarate for ophthalmic diseases","volume":"55","author":"Kimura","year":"2007","journal-title":"Chem. Pharm. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1248\/cpb.c20-00289","article-title":"Prolonged distribution of tranilast in the eyes after topical application onto eyelid skin","volume":"68","author":"See","year":"2020","journal-title":"Chem. Pharm. Bull."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1007\/s10384-024-01070-6","article-title":"Trans-eyelid distribution of epinastine to the conjunctiva following eyelid application in rabbits","volume":"68","author":"Mochizuki","year":"2024","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1089\/jop.2023.0132","article-title":"Epinastine Cream: A Novel Once-Daily Therapeutic Agent for Allergic Conjunctivitis","volume":"40","author":"Ogura","year":"2024","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1111\/j.1398-9995.2011.02676.x","article-title":"Prevalence and impact of rhinitis in asthma. SACRA, a cross-sectional nation-wide study in Japan","volume":"66","author":"Ohta","year":"2011","journal-title":"Allergy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2500\/aap.2011.32.3448","article-title":"Comprehensive report of olopatadine 0.6% nasal spray as treatment for children with seasonal allergic rhinitis","volume":"32","author":"Meltzer","year":"2011","journal-title":"Allergy Asthma Proc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"612","DOI":"10.2500\/aap.2009.30.3298","article-title":"Safety and efficacy of olopatadine hydrochloride nasal spray 0.6% in pediatric subjects with allergic rhinitis","volume":"30","author":"Berger","year":"2009","journal-title":"Allergy Asthma Proc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1586\/eci.09.89","article-title":"Olopatadine nasal spray for the treatment of allergic rhinitis","volume":"6","author":"Roland","year":"2010","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1177\/0194599819832277","article-title":"Epistaxis Risk Associated with Intranasal Corticosteroid Sprays: A Systematic Review and Meta-analysis","volume":"161","author":"Wu","year":"2019","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1097\/00005537-200009000-00025","article-title":"Effects of benzalkonium chloride on innate immunity physiology of the human nasal mucosa in vivo","volume":"110","author":"Storaas","year":"2000","journal-title":"Laryngoscope"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/S0149-2918(99)80053-8","article-title":"Adverse effects of benzalkonium chloride on the nasal mucosa: Allergic rhinitis and rhinitis medicamentosa","volume":"21","author":"Graf","year":"1999","journal-title":"Clin. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1080\/1744666X.2022.2089654","article-title":"Comorbid allergic rhinitis and asthma: Important clinical considerations","volume":"18","author":"Nappi","year":"2022","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1002\/alr.21387","article-title":"Surgery for allergic rhinitis","volume":"4","author":"Chhabra","year":"2014","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e00934-17","DOI":"10.1128\/IAI.00934-17","article-title":"Dysbiosis of Inferior Turbinate Microbiota Is Associated with High Total IgE Levels in Patients with Allergic Rhinitis","volume":"86","author":"Hyun","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/alr.21835","article-title":"Middle turbinate edema as a diagnostic marker of inhalant allergy","volume":"7","author":"Hamizan","year":"2017","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_41","first-page":"59","article-title":"Cough variant asthma: Potential pathophysiology and management","volume":"55","author":"Matsumoto","year":"2006","journal-title":"Allergol. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"932","DOI":"10.3109\/02770903.2013.823444","article-title":"Cough variant and cough-predominant asthma are major causes of persistent cough: A multicenter study in Japan","volume":"50","author":"Niimi","year":"2013","journal-title":"J. Asthma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1164\/rccm.200306-727OC","article-title":"Increased airway vascularity in newly diagnosed asthma using a high-magnification bronchovideoscope","volume":"168","author":"Tanaka","year":"2003","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1111\/j.1440-1843.2010.01859.x","article-title":"Cough challenge tests involving mechanical stimulation of the cervical trachea in patients with cough as a leading symptom","volume":"15","author":"Kamimura","year":"2010","journal-title":"Respirology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"411","DOI":"10.2332\/allergolint.11-OA-0357","article-title":"Superiority of nebulized corticosteroids over dry powder inhalers in certain patients with cough variant asthma or cough-predominant asthma","volume":"61","author":"Kamimura","year":"2012","journal-title":"Allergol. Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.pupt.2004.09.009","article-title":"Cough and asthma","volume":"17","author":"Pavord","year":"2004","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S96","DOI":"10.1016\/S0091-6749(03)01883-9","article-title":"Prospects for antihistamines in the treatment of asthma","volume":"112","author":"Nelson","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/j.1398-9995.2006.01090.x","article-title":"Local oropharyngeal side effects of ICS in patients with asthma","volume":"61","author":"Buhl","year":"2006","journal-title":"Allergy"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/j.1749-4486.2008.01837.x","article-title":"The inflammation produced by corticosteroid inhalers in the pharynx in asthmatics","volume":"33","author":"Bhalla","year":"2008","journal-title":"Clin. Otolaryngol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"457","DOI":"10.5606\/tgkdc.dergisi.2021.21951","article-title":"Percutaneous ultrasound-guided versus bronchoscopy-guided dilatational tracheostomy after median sternotomy: A case-control study","volume":"29","author":"Bermede","year":"2021","journal-title":"Turk. J. Thorac. Cardiovasc. Surg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"110946","DOI":"10.1016\/j.ijporl.2021.110946","article-title":"Measurement of the subglottic diameter of the trachea and its distance from the skin by ultrasonography in children","volume":"150","author":"Uysal","year":"2021","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1007\/s11095-010-0337-x","article-title":"Iontophoresis-facilitated delivery of prednisolone through throat skin to the trachea after topical application of its succinate salt","volume":"28","author":"Ishii","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s12565-020-00552-0","article-title":"The blood supply of the inferior nasal concha (turbinate): A cadaveric anatomical study","volume":"96","author":"Tatar","year":"2021","journal-title":"Anat. Sci. Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.otc.2009.01.008","article-title":"Nasal, septal, and turbinate anatomy and embryology","volume":"42","author":"Neskey","year":"2009","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1097\/SCS.0000000000003389","article-title":"Full-Thickness Entire Nasal Alar Reconstruction Using a Forehead Flap in Asians: No Cartilaginous Infrastructural Lining Is Necessary","volume":"28","author":"Funayama","year":"2017","journal-title":"J. Craniofac. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1034\/j.1600-0536.2003.480105.x","article-title":"Profile of irritant patch testing with detergents: Sodium lauryl sulfate, sodium laureth sulfate and alkyl polyglucoside","volume":"48","author":"Happle","year":"2003","journal-title":"Contact Dermat."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1159\/000093112","article-title":"Sodium lauryl sulfate-induced irritation in the human face: Regional and age-related differences","volume":"19","author":"Marrakchi","year":"2006","journal-title":"Ski. Pharmacol. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0190-9622(83)70024-1","article-title":"Contact dermatitis caused by diphenhydramine hydrochloride","volume":"8","author":"Coskey","year":"1983","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rubegni, G., Padula, T., Calabrese, L., D\u2019Onghia, M., Tognetti, L., Cinotti, E., Lazzeri, L., Ermini, G., Cartocci, A., and Tosi, G.M. (2025). Eyelid Contact Dermatitis: 25-Year Single-Center Retrospective Study. J. Clin. Med., 14.","DOI":"10.3390\/jcm14030823"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1600-0846.1998.tb00112.x","article-title":"The face and neck: Regional variation in skin barrier function and reactivity","volume":"4","author":"Leroy","year":"1998","journal-title":"Ski. Res. Technol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1468-2494.2008.00459.x","article-title":"Location-related differences in structure and function of the stratum corneum with special emphasis on those of the facial skin","volume":"30","author":"Tagami","year":"2008","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1600-0846.2007.00183.x","article-title":"Functional analyses of the eyelid skin constituting the most soft and smooth area on the face: Contribution of its remarkably large superficial corneocytes to effective water-holding capacity of the stratum corneum","volume":"13","author":"Pratchyapruit","year":"2007","journal-title":"Ski. Res. Technol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.1016\/j.xphs.2019.04.012","article-title":"PK and tissue distribution of pilocarpine after application to eyelid skin of rats","volume":"108","author":"See","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.1016\/j.xphs.2024.06.004","article-title":"Physiologically Based Pharmacokinetic Modeling and Clinical Extrapolation for Topical Application of Pilocarpine on Eyelids: A Comprehensive Study","volume":"113","author":"Lin","year":"2024","journal-title":"J. Pharm. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e2302375","DOI":"10.1002\/adhm.202302375","article-title":"Advancements in Skin-Mediated Drug Delivery: Mechanisms, Techniques, and Applications","volume":"13","author":"Lee","year":"2024","journal-title":"Adv. Healthc. Mater."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/7\/867\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:02:55Z","timestamp":1760032975000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/7\/867"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,2]]},"references-count":65,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["pharmaceutics17070867"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17070867","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,2]]}}}