{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:16:42Z","timestamp":1776745002030,"version":"3.51.2"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T00:00:00Z","timestamp":1630195200000},"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>The currently available antifungal therapy for oral candidiasis (OC) has various limitations restricting its clinical use, such as short retention time, suboptimal drug concentration and low patients compliance. These issues could be overcome using micro or nanotechnology. In particular, solid lipid microparticles (SLMs) resulted as a particularly promising penetration enhancer carrier for lipophilic drugs, such as the antifungal miconazole (MCZ). Based on these considerations, cetyl decanoate (here synthesized without the use of metal catalysis) was employed together with 1-hexadecanol to prepare MCZ-loaded SLMs. These resulted in a powder composed of 45\u2013300 \u00b5m diameter solid spherical particles, able to load a high amount of MCZ in the amorphous form and characterized by a melting temperature range perfectly compatible with oromucosal administration (35\u201337 \u00b0C). Moreover, when compared to Daktarin\u00ae 2% oral gel in ex vivo experiments, SLMs were able to increase up to three-fold MCZ accumulation into the porcine buccal mucosa. The prepared SLMs were then loaded into a buccal gel or a microcomposite mucoadhesive buccal film and evaluated in terms of MCZ permeation and\/or accumulation into porcine buccal mucosa by using lower doses than the conventional dosage form. The promising results obtained highlighted an enhancement in terms of MCZ accumulation even at low doses. Furthermore, the prepared buccal film was eligible as stable, reproducible and also highly mucoadhesive. Therefore, the formulated SLMs represent a penetration enhancer vehicle suitable to reduce the dose of lipophilic drugs to be administered to achieve the desired therapeutic effects, as well as being able to be effectively embedded into easily administrable solid or semisolid dosage forms.<\/jats:p>","DOI":"10.3390\/pharmaceutics13091361","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T04:07:28Z","timestamp":1630382848000},"page":"1361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Solid and Semisolid Innovative Formulations Containing Miconazole-Loaded Solid Lipid Microparticles to Promote Drug Entrapment into the Buccal Mucosa"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5186-1244","authenticated-orcid":false,"given":"Viviana","family":"De Caro","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libero Italo","family":"Giannola","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-2704","authenticated-orcid":false,"given":"Giulia","family":"Di Prima","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/odi.12380","article-title":"Efficacy and safety of miconazole for oral candidiasis: A systematic review and meta-analysis","volume":"22","author":"Zhang","year":"2016","journal-title":"Oral Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1002\/eji.201344403","article-title":"Richness and diversity of mammalian fungal communities shape innate and adaptive immunity in health and disease","volume":"44","author":"Rizzetto","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.4103\/0973-029X.141325","article-title":"Oral candidiasis: An overview","volume":"18","author":"Agrawal","year":"2014","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/j.1600-0757.2008.00291.x","article-title":"Oral mucosal fungal infections","volume":"49","author":"Samaranayake","year":"2009","journal-title":"Periodontology 2000"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s10266-009-0118-3","article-title":"Antifungal drug resistance of oral fungi","volume":"98","author":"Niimi","year":"2010","journal-title":"Odontology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"328","DOI":"10.3109\/1040841X.2011.585606","article-title":"Oral candidosis\u2014Clinical challenges of a biofilm disease","volume":"37","author":"Rautemaa","year":"2011","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1093\/cid\/cis205","article-title":"Miconazole Mucoadhesive Tablets: A Novel Delivery System","volume":"54","author":"Vazquez","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/j.1439-0507.2009.01728.x","article-title":"Antifungal activity of miconazole against recent Candida strains","volume":"53","author":"Isham","year":"2010","journal-title":"Mycoses"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Diaz-Salmeron, R., Toussaint, B., Huang, N., Bourgeois Ducournau, E., Alviset, G., Goulay Dufa\u00ff, S., Hillaireau, H., Dufa\u00ff Wojcicki, A., and Boudy, V. (2021). Mucoadhesive poloxamer-based hydrogels for the release of HP-\u03b2-cd-complexed dexamethasone in the treatment of buccal diseases. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010117"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s13346-021-00905-w","article-title":"Nanocomposite systems for precise oral delivery of drugs and biologics","volume":"11","author":"Andretto","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1517\/17425247.2.1.75","article-title":"Solid lipid microparticles: Formulation, preparation, characterisation, drug release and applications","volume":"2","author":"Jaspart","year":"2005","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.chemphyslip.2012.01.007","article-title":"Lipospheres and pro-nano lipospheres for delivery of poorly water soluble compounds","volume":"165","author":"Elgart","year":"2012","journal-title":"Chem. Phys. Lipids"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1517\/17425247.2015.980812","article-title":"Solid lipid microparticles as an approach to drug delivery","volume":"12","author":"Scalia","year":"2015","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2174\/156720110790396454","article-title":"Development of taste masked fast disintegrating films of levocetirizine dihydrochloride for oral use","volume":"7","author":"Mahesh","year":"2010","journal-title":"Curr. Drug Deliv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4103\/0250-474X.40330","article-title":"Formulation and characterization of mucoadhesive buccal films of glipizide","volume":"70","author":"Semalty","year":"2008","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.3109\/03639045.2014.971030","article-title":"Aloin delivery on buccal mucosa: Ex vivo studies and design of a new locoregional dosing system","volume":"41","author":"Scaturro","year":"2015","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1208\/s12249-018-1202-1","article-title":"Mucoadhesive Polymeric Films to Enhance Barbaloin Penetration Into Buccal Mucosa: A Novel Approach to Chemoprevention","volume":"20","author":"Conigliaro","year":"2019","journal-title":"AAPS PharmSciTech"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ejpb.2007.02.020","article-title":"Release of naltrexone on buccal mucosa: Permeation studies, histological aspects and matrix system design","volume":"67","author":"Giannola","year":"2007","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D503","DOI":"10.1051\/ocl\/2018036","article-title":"Augmented bio-based lipids for cosmetics","volume":"25","author":"Guilbot","year":"2018","journal-title":"OCL"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.4028\/www.scientific.net\/MSF.539-543.2317","article-title":"Multi-Valent Metal Salt Hydrates as Catalysts for the Esterification of Fatty Acids and Alcohols","volume":"539\u2013543","author":"Mantri","year":"2007","journal-title":"Mater. Sci. Forum"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6962","DOI":"10.1016\/j.tetlet.2007.07.159","article-title":"Liquid\u2013liquid biphasic synthesis of long chain wax esters using the Lewis acidic ionic liquid choline chloride\u00b72ZnCl2","volume":"48","author":"Sunitha","year":"2007","journal-title":"Tetrahedron Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1039\/b504369g","article-title":"ZrOCl2\u00b78H2O catalysts for the esterification of long chain aliphatic carboxylic acids and alcohols. The enhancement of catalytic performance by supporting on ordered mesoporous silica","volume":"7","author":"Mantri","year":"2005","journal-title":"Green Chem."},{"key":"ref_23","first-page":"2933","article-title":"Ester Synthesis by Crude Lipase Preparation from Pseudomonas fragi 22.39 B in n-Hexane","volume":"52","author":"Nishio","year":"1988","journal-title":"Agric. Biol. Chem."},{"key":"ref_24","first-page":"917","article-title":"In vitro evaluation of cumulative release of valproic acid and vitamin E from hexadecanol microspheres. Part 2: Antiepileptic agents","volume":"48","author":"Giannola","year":"1993","journal-title":"Pharmazie"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Angellotti, G., Murgia, D., Presentato, A., D\u2019Oca, M.C., Scarpaci, A.G., Alduina, R., Raimondi, M.V., and De Caro, V. (2020). Antibacterial PEGylated Solid Lipid Microparticles for Cosmeceutical Purpose: Formulation, Characterization, and Efficacy Evaluation. Materials, 13.","DOI":"10.3390\/ma13092073"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0378-5173(02)00081-9","article-title":"Preparation of solid lipid nanoparticles with clobetasol propionate by a novel solvent diffusion method in aqueous system and physicochemical characterization","volume":"239","author":"Hu","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3609","DOI":"10.1021\/acs.molpharmaceut.0c00666","article-title":"Solid Lipid Microparticles for Oral Delivery of Catalase: Focus on the Protein Structural Integrity and Gastric Protection","volume":"17","author":"Bertoni","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_28","first-page":"183","article-title":"Polycaprolactone scaffold engineered for sustained release of resveratrol: Therapeutic enhancement in bone tissue engineering","volume":"9","author":"Kamath","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1186\/1556-276X-8-386","article-title":"Characteristics of lipid micro- and nanoparticles based on supercritical formation for potential pharmaceutical application","volume":"8","author":"Santo","year":"2013","journal-title":"Nanoscale Res. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ijpharm.2012.03.022","article-title":"New prospective in treatment of Parkinson\u2019s disease: Studies on permeation of ropinirole through buccal mucosa","volume":"429","author":"Giandalia","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Arai, K., and Shikata, T. (2020). Hydration\/dehydration behavior of hydroxyethyl cellulose ether in aqueous solution. Molecules, 25.","DOI":"10.3390\/molecules25204726"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"102046","DOI":"10.1016\/j.jddst.2020.102046","article-title":"Pharmaceutical assessment of polyvinylpyrrolidone (PVP): As excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition","volume":"60","author":"Kurakula","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"De Caro, V., Murgia, D., Seidita, F., Bologna, E., Alotta, G., Zingales, M., and Campisi, G. (2019). Enhanced In Situ Availability of Aphanizomenon Flos-Aquae Constituents Entrapped in Buccal Films for the Treatment of Oxidative Stress-Related Oral Diseases: Biomechanical Characterization and In Vitro\/Ex Vivo Evaluation. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11010035"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1002\/jps.22458","article-title":"Trehalose: Current Use and Future Applications","volume":"100","author":"Ohtake","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5877","DOI":"10.1128\/IAI.00624-06","article-title":"Characterization and Regulation of the Trehalose Synthesis Pathway and Its Importance in the Pathogenicity of Cryptococcus neoformans","volume":"74","author":"Petzold","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e01719-20","DOI":"10.1128\/AAC.01719-20","article-title":"The Future of Antifungal Drug Therapy: Novel Compounds and Targets","volume":"65","author":"Dasilva","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Di Prima, G., Campisi, G., and De Caro, V. (2020). Amorphous Ropinirole-Loaded Mucoadhesive Buccal Film: A Potential Patient-Friendly Tool to Improve Drug Pharmacokinetic Profile and Effectiveness. J. Pers. Med., 10.","DOI":"10.3390\/jpm10040242"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jconrel.2012.11.019","article-title":"In vitro techniques to evaluate buccal films","volume":"166","author":"Nair","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1179\/2295333714Y.0000000089","article-title":"Miconazole buccal gel and risk for systemic bleeding: How certain topical formula can interfere with anticoagulants","volume":"70","year":"2015","journal-title":"Acta Clin. Belg."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/9\/1361\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:54:55Z","timestamp":1760165695000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/9\/1361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,29]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["pharmaceutics13091361"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13091361","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,29]]}}}