{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:26:50Z","timestamp":1785432410580,"version":"3.56.0"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Ha\u2019il","award":["RG-24 072"],"award-info":[{"award-number":["RG-24 072"]}]},{"award":["RG-24 072"],"award-info":[{"award-number":["RG-24 072"]}],"id":[{"id":"https:\/\/ror.org\/013w98a82","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical formulations. Additionally, oral KTZ has been subject to labeling restrictions and market withdrawal due to its association with severe hepatic adverse effects. This study was conducted to design, optimize, and evaluate KTZ-loaded nanolipid carriers (NLCs; KTZ-NLCs) as a delivery platform that could improve cutaneous bioavailability and enhance antifungal activity. Methods: The optimized KTZ-NLCs were further incorporated into a mucoadhesive system (KTZ-NLCs-C) through the inclusion of Carbopol\u00ae 940 NF, aiming to improve the retention of the formulation on the skin surface. NLCs were characterized in terms of their physical appearance, particle size, polydispersity index, zeta potential, pH, viscosity, drug content, and entrapment efficiency. The optimized KTZ-NLC and KTZ-NLCs-C formulations were subsequently assessed for in vitro drug release, ex vivo skin permeation and deposition, as well as in vivo skin irritation. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KTZ over 24 h. The ex vivo transdermal flux and permeability coefficient of KTZ from the lead KTZ-NLCs-C formulation were approximately 2.8-fold greater than those achieved with the marketed cream formulation. The in vivo skin irritation studies indicate that NLC-based formulations are suitable for topical applications. The lead formulation was stable for 90 days (the final time point evaluated) under refrigerated and room-temperature storage conditions. Conclusions: These findings suggest that the NLC-based system is a promising platform for the topical delivery of KTZ and has the potential to enhance the therapeutic outcomes for patients with superficial fungal infections.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060753","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:52:11Z","timestamp":1782453131000},"page":"753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mucoadhesive Nanostructured Lipid Carriers of Ketoconazole for Enhanced Dermal Delivery and Antifungal Activity: Formulation Optimization and In Vivo Evaluation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-5128","authenticated-orcid":false,"given":"Mashan","family":"Almutairi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Adel Ali","family":"Youssef","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0450-9846","authenticated-orcid":false,"given":"Yazed S.","family":"Alsowaida","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Alobaida","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3807-1299","authenticated-orcid":false,"given":"Samir A.","family":"Ross","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS 38677, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hay, R. (2018). Therapy of Skin, Hair and Nail Fungal Infections. J. Fungi, 4.","DOI":"10.3390\/jof4030099"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1177\/1203475415574970","article-title":"The Rise and Fall of Oral Ketoconazole","volume":"19","author":"Gupta","year":"2015","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1080\/09546634.2019.1573309","article-title":"Topical Ketoconazole: A Systematic Review of Current Dermatological Applications and Future Developments","volume":"30","author":"Choi","year":"2019","journal-title":"J. Dermatol. Treat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/infdis\/138.2.245","article-title":"Comparison of the in Vitro Antifungal Activities of Miconazole and a New Imidazole, R41, 400","volume":"138","author":"Dixon","year":"1978","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/jac\/6.1.97","article-title":"The Activity in Vitro and in Vivo of a New Imidazole Antifungal, Ketoconazole","volume":"6","author":"Odds","year":"1980","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1021\/jm00194a023","article-title":"Antimycotic Imidazoles. Part 4. Synthesis and Antifungal Activity of Ketoconazole, a New Potent Orally Active Broad-Spectrum Antifungal Agent","volume":"22","author":"Heeres","year":"1979","journal-title":"J. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1007\/BF01960348","article-title":"Ketoconazole\u2014A New Broad Spectrum Orally Active Antimycotic","volume":"35","author":"Thienpont","year":"1979","journal-title":"Experientia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.xphs.2017.09.002","article-title":"The Combination of GIS and Biphasic to Better Predict In Vivo Dissolution of BCS Class IIb Drugs, Ketoconazole and Raloxifene","volume":"107","author":"Tsume","year":"2018","journal-title":"J. Pharm. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1007\/s13346-021-01058-6","article-title":"In Vitro Release, Ex Vivo Penetration, and in Vivo Dermatokinetics of Ketoconazole-Loaded Solid Lipid Nanoparticles for Topical Delivery","volume":"12","author":"Ramzan","year":"2022","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s10856-015-5487-2","article-title":"Skin Targeted Lipid Vesicles as Novel Nano-Carrier of Ketoconazole: Characterization, in Vitro and in Vivo Evaluation","volume":"26","author":"Guo","year":"2015","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.pharep.2018.10.008","article-title":"Nanostructured Lipid Carriers: A Potential Use for Skin Drug Delivery Systems","volume":"71","author":"Szekalska","year":"2019","journal-title":"Pharmacol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.nano.2015.09.004","article-title":"Nanostructured Lipid Carriers: Promising Drug Delivery Systems for Future Clinics","volume":"12","author":"Beloqui","year":"2016","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104981","DOI":"10.1016\/j.chemphyslip.2020.104981","article-title":"Colloidal Lipid Nanodispersion Enriched Hydrogel of Antifungal Agent for Management of Fungal Infections: Comparative in-Vitro, Ex-Vivo and in-Vivo Evaluation for Oral and Topical Application","volume":"233","author":"Dudhipala","year":"2020","journal-title":"Chem. Phys. Lipids"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Joshi, P.H., Youssef, A.A.A., Ghonge, M., Varner, C., Tripathi, S., Dudhipala, N., and Majumdar, S. (2023). Gatifloxacin Loaded Nano Lipid Carriers for the Management of Bacterial Conjunctivitis. Antibiotics, 12.","DOI":"10.3390\/antibiotics12081318"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1007\/s13346-020-00744-1","article-title":"Critical Quality Attributes in the Development of Therapeutic Nanomedicines toward Clinical Translation","volume":"10","author":"Taha","year":"2020","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ijpharm.2017.06.042","article-title":"Ocular Disposition of Ciprofloxacin from Topical, PEGylated Nanostructured Lipid Carriers: Effect of Molecular Weight and Density of Poly (Ethylene) Glycol","volume":"529","author":"Balguri","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Youssef, A.A.A., Thakkar, R., Senapati, S., Joshi, P.H., Dudhipala, N., and Majumdar, S. (2022). Design of Topical Moxifloxacin Mucoadhesive Nanoemulsion for the Management of Ocular Bacterial Infections. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061246"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Youssef, A., Dudhipala, N., and Majumdar, S. (2020). Ciprofloxacin Loaded Nanostructured Lipid Carriers Incorporated into In-Situ Gels to Improve Management of Bacterial Endophthalmitis. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12060572"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sadozai, S.K., Khan, S.A., Baseer, A., Ullah, R., Zeb, A., and Schneider, M. (2022). In Vitro, Ex Vivo, and in Vivo Evaluation of Nanoparticle-Based Topical Formulation against Candida Albicans Infection. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.909851"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Almutairi, M., Youssef, A.A.A., Subaiea, G.M., Alobaida, A., and Almuntashiri, S. (2026). Keto-conazole-Loaded Mucoadhesive Nanoemulsions for the Better Management of Topical Fungal Infections: Optimization, In Vitro, Ex Vivo, and In Vivo Assessments. Pharmaceutics, 18.","DOI":"10.20944\/preprints202604.0206.v1"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ijpharm.2009.05.019","article-title":"Microemulsion-Based Hydrogel Formulation of Penciclovir for Topical Delivery","volume":"378","author":"Zhu","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"148","DOI":"10.2174\/2211738508666200225113359","article-title":"Enhanced Pharmacokinetic Activity of Zotepine via Nanostructured Lipid Carrier System in Wistar Rats for Oral Application","volume":"8","author":"Tirumalesh","year":"2020","journal-title":"Pharm. Nanotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Senapati, S., Youssef, A.A.A., Sweeney, C., Cai, C., Dudhipala, N., and Majumdar, S. (2022). Cannabidiol Loaded Topical Ophthalmic Nanoemulsion Lowers Intraocular Pressure in Normotensive Dutch-Belted Rabbits. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122585"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1016\/j.xphs.2018.04.014","article-title":"Formulation Development, Optimization, and In Vitro\u2013In Vivo Characterization of Natamycin-Loaded PEGylated Nano-Lipid Carriers for Ocular Applications","volume":"107","author":"Patil","year":"2018","journal-title":"J. Pharm. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"113734","DOI":"10.1016\/j.molliq.2020.113734","article-title":"Impact of Liquid Lipid on Development and Stability of Trimyristin Nanostructured Lipid Carriers for Oral Delivery of Resveratrol","volume":"316","author":"Houacine","year":"2020","journal-title":"J. Mol. Liq."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ijpharm.2016.12.010","article-title":"Quality by Design (QbD)-Enabled Development of Aceclofenac Loaded-Nano Structured Lipid Carriers (NLCs): An Improved Dermatokinetic Profile for Inflammatory Disorder(s)","volume":"517","author":"Garg","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s13204-015-0434-6","article-title":"Development and Optimization of Ifosfamide Nanostructured Lipid Carriers for Oral Delivery Using Response Surface Methodology","volume":"6","author":"Velmurugan","year":"2016","journal-title":"Appl. Nanosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"42013","DOI":"10.1038\/s41598-025-26860-x","article-title":"Development and Optimization of Moxifloxacin Solid Lipid Nanoparticles via Double Emulsion Organic Solvent Free Technique Applying Box\u2013Behnken Experimental Design","volume":"15","author":"Elshazly","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.2147\/IJN.S190502","article-title":"Natamycin Solid Lipid Nanoparticles\u2014Sustained Ocular Delivery System of Higher Corneal Penetration against Deep Fungal Keratitis: Preparation and Optimization","volume":"14","author":"Khames","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.petrol.2015.03.008","article-title":"Modeling the Steady-Shear Rheological Behavior of Dilute to Highly Concentrated Oil-in-Water (o\/w) Emulsions: Effect of Temperature, Oil Volume Fraction and Anionic Surfactant Concentration","volume":"129","author":"Kundu","year":"2015","journal-title":"J. Pet. Sci. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109857","DOI":"10.1016\/j.petrol.2021.109857","article-title":"Effect of Oil\/Water Ratio on Rheological Behavior, Droplet Size, Zeta Potential, Long-Term Stability, and Acid-Induced Demulsification of Crude Oil\/Water Nanoemulsions","volume":"209","author":"Onaizi","year":"2021","journal-title":"J. Pet. Sci. Eng."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1080\/10837450.2019.1596133","article-title":"Cyproterone Acetate-Loaded Nanostructured Lipid Carriers: Effect of Particle Size on Skin Penetration and Follicular Targeting","volume":"24","author":"Ghasemiyeh","year":"2019","journal-title":"Pharm. Dev. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shimojo, A.A.M., Fernandes, A.R.V., Ferreira, N.R.E., Sanchez-Lopez, E., Santana, M.H.A., and Souto, E.B. (2019). Evaluation of the Influence of Process Parameters on the Properties of Resveratrol-Loaded NLC Using 22 Full Factorial Design. Antioxidants, 8.","DOI":"10.3390\/antiox8080272"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.2174\/1389200221666200719003304","article-title":"Nanostructured Lipid Carriers (NLCs): Nose-to-Brain Delivery and Theranostic Application","volume":"21","author":"Ahmad","year":"2020","journal-title":"Curr. Drug Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1208\/s12249-020-1620-8","article-title":"Bromocriptine Nanoemulsion-Loaded Transdermal Gel: Optimization Using Factorial Design, In Vitro and In Vivo Evaluation","volume":"21","author":"Sita","year":"2020","journal-title":"AAPS PharmSciTech"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1600-0536.1995.tb00470.x","article-title":"Surfactants and Experimental Irritant Contact Dermatitis","volume":"33","author":"Effendy","year":"1995","journal-title":"Contact Dermat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"121564","DOI":"10.1016\/j.ijpharm.2022.121564","article-title":"Impact of Mucoadhesive Agent Inclusion on the Intraocular Pressure Lowering Profile of \u03949-Tetrahydrocannabinol-Valine-Hemisuccinate Loaded Nanoemulsions in New Zealand White Rabbits","volume":"616","author":"Sweeney","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.2147\/DDDT.S264648","article-title":"Potential of Nanoparticles as Permeation Enhancers and Targeted Delivery Options for Skin: Advantages and Disadvantages","volume":"14","author":"Ghasemiyeh","year":"2020","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.ijpharm.2014.10.067","article-title":"A New Topical Formulation for Psoriasis: Development of Methotrexate-Loaded Nanostructured Lipid Carriers","volume":"477","author":"Pinto","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18012","DOI":"10.1038\/s41598-023-43689-4","article-title":"Application of Ensemble Machine Learning Approach to Assess the Factors Affecting Size and Polydispersity Index of Liposomal Nanoparticles","volume":"13","author":"Hoseini","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ijpharm.2011.05.008","article-title":"Lipid Nanocarriers for Dermal Delivery of Lutein: Preparation, Characterization, Stability and Performance","volume":"414","author":"Mitri","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ijpharm.2006.01.040","article-title":"Preparation and Characteristics of Monostearin Nanostructured Lipid Carriers","volume":"314","author":"Hu","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/srt.12709","article-title":"The Role of Viscosity on Skin Penetration from Cellulose Ether-Based Hydrogels","volume":"25","author":"Binder","year":"2019","journal-title":"Skin Res. Technol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jddst.2015.05.006","article-title":"Cocrystals of Itraconazole with Amino Acids: Screening, Synthesis, Solid State Characterization, in Vitro Drug Release and Antifungal Activity","volume":"28","author":"Shete","year":"2015","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.colsurfb.2017.11.064","article-title":"Nanostructured Lipid Carriers for Improved Oral Delivery and Prolonged Antihyperlipidemic Effect of Simvastatin","volume":"162","author":"Fathi","year":"2018","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"102928","DOI":"10.1016\/j.jddst.2021.102928","article-title":"Development and Characterization of Novel Topical Oil\/PEG Creams of Voriconazole for the Treatment of Fungal Infections","volume":"66","author":"Shettar","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ferreira, K.C.B., Valle, A.B.C.d.S., Paes, C.Q., Tavares, G.D., and Pittella, F. (2021). Nanostructured Lipid Carriers for the Formulation of Topical Anti-Inflammatory Nanomedicines Based on Natural Substances. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091454"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.lfs.2013.09.027","article-title":"Development and Characterization of a Novel Controlled Release Drug Delivery System Based on Nanostructured Lipid Carriers Gel for Meloxicam","volume":"93","author":"Khurana","year":"2013","journal-title":"Life Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Shaker, D.S., Ishak, R.A.H., Ghoneim, A., and Elhuoni, M.A. (2019). Nanoemulsion: A Review on Mechanisms for the Transdermal Delivery of Hydrophobic and Hydrophilic Drugs. Sci. Pharm., 87.","DOI":"10.3390\/scipharm87030017"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1248\/bpb.26.66","article-title":"Examination of the Mechanism of Oleic Acid-Induced Percutaneous Penetration Enhancement: An Ultrastructural Study","volume":"26","author":"Jiang","year":"2003","journal-title":"Biol. Pharm. Bull."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/6\/753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T06:01:05Z","timestamp":1782453665000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/6\/753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,19]]},"references-count":50,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["pharmaceutics18060753"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18060753","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,19]]}}}