{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T05:23:02Z","timestamp":1793856182670,"version":"4.6.1"},"reference-count":44,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005668","name":"Brazilian agency Funda\u00e7\u00e3o de Apoio \u00e0 Pesquisa do Distrito Federal (FAPDF)","doi-asserted-by":"publisher","award":["00193-00000804\/2021-95"],"award-info":[{"award-number":["00193-00000804\/2021-95"]}],"id":[{"id":"10.13039\/501100005668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005668","name":"Brazilian agency Funda\u00e7\u00e3o de Apoio \u00e0 Pesquisa do Distrito Federal (FAPDF)","doi-asserted-by":"publisher","award":["Edital DPI\/DPG 02\/2023"],"award-info":[{"award-number":["Edital DPI\/DPG 02\/2023"]}],"id":[{"id":"10.13039\/501100005668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008994","name":"University of Brasilia","doi-asserted-by":"publisher","award":["00193-00000804\/2021-95"],"award-info":[{"award-number":["00193-00000804\/2021-95"]}],"id":[{"id":"10.13039\/100008994","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008994","name":"University of Brasilia","doi-asserted-by":"publisher","award":["Edital DPI\/DPG 02\/2023"],"award-info":[{"award-number":["Edital DPI\/DPG 02\/2023"]}],"id":[{"id":"10.13039\/100008994","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid and a substance controlling hair loss progression could reduce or eliminate such adverse effects and increase the patient\u2019s adherence to the treatment, this study prepares polymeric and lipidic nanoparticles (PNPs and NLCs) to co-entrap minoxidil and betamethasone and compares the follicular drug delivery provided by topical application of these nanoparticles. The prepared PNPs loaded 99.1 \u00b1 13.0% minoxidil and 70.2 \u00b1 12.8% betamethasone, while the NLCs entrapped 99.4 \u00b1 0.1 minoxidil and 80.7 \u00b1 0.1% betamethasone. PNPs and NLCs presented diameters in the same range, varying from 414 \u00b1 10 nm to 567 \u00b1 30 nm. The thermal analysis revealed that the production conditions favor the solubilization of the drugs in the nanoparticles, preserving their stability. In in vitro permeation studies with porcine skin, PNPs provided a 2.6-fold increase in minoxidil penetration into the follicular casts compared to the control and no remarkable difference in terms of betamethasone; in contrast, NLCs provided a significant (specifically, a tenfold) increase in minoxidil penetration into the hair follicles compared to the control, and they delivered higher concentrations of betamethasone in hair follicles than both PNPs and the control. Neither PNPs nor NLCs promoted transdermal permeation of the drugs to the receptor solution, which should favor a topical therapy. Furthermore, both nanoparticles targeted approximately 50% of minoxidil delivery to the follicular casts and NLCs targeted 74% of betamethasone delivery to the hair follicles. In conclusion, PNPs and NLCs are promising drug delivery systems for enhancing follicular targeting of drugs, but NLCs showed superior performance for lipophilic drugs.<\/jats:p>","DOI":"10.3390\/ph16091322","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T23:11:52Z","timestamp":1695165112000},"page":"1322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Follicle-Targeted Delivery of Betamethasone and Minoxidil Co-Entrapped in Polymeric and Lipid Nanoparticles for Topical Alopecia Areata Treatment"],"prefix":"10.3390","volume":"16","author":[{"given":"Breno N.","family":"Matos","sequence":"first","affiliation":[{"name":"Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Bras\u00edlia, Brasilia 70910-900, DF, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2177-8941","authenticated-orcid":false,"given":"Ana Luiza","family":"Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Bras\u00edlia, Brasilia 70910-900, DF, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila O.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Bras\u00edlia, Brasilia 70910-900, DF, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9167-6852","authenticated-orcid":false,"given":"Marcilio","family":"Cunha-Filho","sequence":"additional","affiliation":[{"name":"Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Bras\u00edlia, Brasilia 70910-900, DF, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6481-2364","authenticated-orcid":false,"given":"Tais","family":"Gratieri","sequence":"additional","affiliation":[{"name":"Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Bras\u00edlia, Brasilia 70910-900, DF, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1924-7885","authenticated-orcid":false,"given":"Guilherme M.","family":"Gelfuso","sequence":"additional","affiliation":[{"name":"Laboratory of Food, Drugs, and Cosmetics (LTMAC), University of Bras\u00edlia, Brasilia 70910-900, DF, Brazil"},{"name":"School of Heath Sciences, Campus Universit\u00e1rio Darcy Ribeiro, s\/n, Brasilia 70910-900, DF, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaad.2017.04.1141","article-title":"Alopecia areata: Disease characteristics, clinical evaluation, and new perspectives on pathogenesis","volume":"78","author":"Strazzulla","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.jaad.2019.08.032","article-title":"Epidemiology of alopecia areata, ophiasis, totalis, and universalis: A systematic review and meta-analysis","volume":"82","author":"Lee","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/ajd.12941","article-title":"Treatment of alopecia areata: An Australian expert consensus statement","volume":"60","author":"Cranwell","year":"2019","journal-title":"Australas. J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1111\/jdv.15545","article-title":"Minoxidil for patchy alopecia areata: Systematic review and meta-analysis","volume":"33","author":"Freire","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.4103\/ijt.ijt_14_18","article-title":"Mesalazine in the Treatment of Extensive Alopecia Areata: A New Therapeutic Option?","volume":"10","author":"Kiszewski","year":"2018","journal-title":"Int. J. Trichol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"485","DOI":"10.2147\/CCID.S284435","article-title":"Topical treatment for scarring and non-scarring alopecia: An overview of the current evidence","volume":"14","author":"Cardoso","year":"2021","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jaad.2020.06.1009","article-title":"Oral minoxidil treatment for hair loss: A review of efficacy and safety","volume":"84","author":"Randolph","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1164\/rccm.201904-0903SO","article-title":"Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management","volume":"201","author":"Bleecker","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41573-023-00670-0","article-title":"Overcoming barriers to patient adherence: The case for developing innovative drug delivery systems","volume":"22","author":"Baryakova","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ijbiomac.2015.01.036","article-title":"Chitosan nanoparticles for targeting and sustaining minoxidil sulphate delivery to hair follicles","volume":"75","author":"Matos","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jconrel.2010.11.015","article-title":"Selective follicular targeting by modification of the particle sizes","volume":"150","author":"Patzelt","year":"2011","journal-title":"J. Control Release"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ijbiomac.2020.02.143","article-title":"Dutasteride nanocapsules for hair follicle targeting: Effect of chitosan-coating and physical stimulus","volume":"151","author":"Ushirobira","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"112101","DOI":"10.1016\/j.colsurfb.2021.112101","article-title":"Follicular-targeted delivery of spironolactone provided by polymeric nanoparticles","volume":"208","author":"Gratieri","year":"2021","journal-title":"Colloids Surf. B"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111448","DOI":"10.1016\/j.colsurfb.2020.111448","article-title":"Nanostructured lipid carriers for hair follicle-targeted delivery of clindamycin and rifampicin to hidradenitis suppurativa treatment","volume":"197","author":"Pereira","year":"2021","journal-title":"Colloids Surf. B"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"117295","DOI":"10.1016\/j.carbpol.2020.117295","article-title":"Targeted clindamycin delivery to pilosebaceous units by chitosan or hyaluronic acid nanoparticles for improved topical treatment of acne vulgaris","volume":"253","author":"Tolentino","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ejpb.2022.02.003","article-title":"Nanostructured lipid carriers loaded with an association of minoxidil and latanoprost for targeted topical therapy of alopecia","volume":"172","author":"Oliveira","year":"2022","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ijpharm.2009.04.001","article-title":"Polymeric nanoparticles encapsulating betamethasone phosphate with different release profiles and stealthiness","volume":"375","author":"Ishihara","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0168-3659(04)00167-1","article-title":"Transdermal delivery of mixnoxidil with block copolymer nanoparticles","volume":"97","author":"Shim","year":"2004","journal-title":"JCR"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Santos, A.C., Pereira-Silva, M., Guerra, C., Costa, D., Peixoto, D., Pereira, I., Pita, I., Ribeiro, A.J., and Veiga, F. (2020). Topical Minoxidil-Loaded Nanotechnology Strategies for Alopecia. Cosmetics, 7.","DOI":"10.3390\/cosmetics7020021"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ijpharm.2015.07.044","article-title":"Polymeric nanoparticles modified with fatty acids encapsulating betamethasone for anti-inflammatory treatment","volume":"493","author":"Silva","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"288","DOI":"10.4103\/1735-5362.235156","article-title":"Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: Applications, advantages and disadvantages","volume":"13","author":"Ghasemiyeh","year":"2018","journal-title":"Res. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1007\/s13346-017-0422-3","article-title":"Preparation of polycaprolactone nanoparticles via supercritical carbon dioxide extraction of emulsions","volume":"8","author":"Ajiboye","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.msec.2018.12.005","article-title":"Encapsulation of geranyl cinnamate in polycaprolactone nanoparticles","volume":"97","author":"Zanetti","year":"2018","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/1871523017666181115104159","article-title":"Development of Betamethasone Dipropionate-Loaded Nanostructured Lipid Carriers for Topical and Transdermal Delivery","volume":"18","author":"Hanna","year":"2019","journal-title":"Antiinflamm. Antiallergy Agents Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.cis.2011.02.005","article-title":"Influence of process and formulation parameters on the formation of submicron particles by solvent displacement and emulsification-diffusion methods: Critical comparison","volume":"163","author":"Fessi","year":"2011","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"411","DOI":"10.5650\/jos.60.411","article-title":"Oleic acid-based gemini surfactants with carboxylic acid headgroups","volume":"60","author":"Sakai","year":"2011","journal-title":"J. Oleo Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1080\/0265204021000058456","article-title":"The characteristics of betamethasone-loaded chitosan microparticles by spray-drying method","volume":"20","author":"Huang","year":"2003","journal-title":"J. Microencapsul."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.2042-7158.1977.tb11275.x","article-title":"Pharmaceutical suspensions: Micro electrophoretic properties","volume":"29","author":"Kayes","year":"1977","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.lwt.2017.09.008","article-title":"Optimization of the emulsification-diffusion method using ultrasound to prepare nanocapsules of different food-core oils","volume":"87","year":"2018","journal-title":"LWT Food Sci. Technol."},{"key":"ref_30","unstructured":"Hansch, C., Leo, A., and Hoekman, D. (1995). Exploring QSAR: Hydrophobic, Electronic, Steric Constants, ACS."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"141906","DOI":"10.1016\/j.cej.2023.141906","article-title":"Thermal decomposition, flame propagation, and combustion reactions behaviours of stearic acid by experiments and molecular dynamic simulation","volume":"461","author":"Li","year":"2023","journal-title":"Chem. Eng. J."},{"key":"ref_32","first-page":"720157","article-title":"Characterization of the polycaprolactone melt crystallization: Complementary optical microscopy, DSC, and AFM studies","volume":"214","author":"Speranza","year":"2014","journal-title":"Sci. World J."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tenorio-Alfonso, A., V\u00e1zquez Ramos, E., Mart\u00ednez, I., Ambrosi, M., and Raudino, M. (2023). Assessment of the structures contribution (crystalline and mesophases) and mechanical properties of polycaprolactone\/pluronic blends. J. Mech. Behav. Biomed. Mater., 139.","DOI":"10.1016\/j.jmbbm.2023.105668"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13809","DOI":"10.1038\/srep13809","article-title":"Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications","volume":"5","author":"Campos","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_35","first-page":"1231","article-title":"Lipid nanoparticles for topical and transdermal application for alopecia treatment: Development, physicochemical characterization, and in vitro release and penetration studies","volume":"9","author":"Gomes","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1080\/03639045.2017.1386204","article-title":"Topical phenytoin nanostructured lipid carriers: Design and development","volume":"44","author":"Motawea","year":"2018","journal-title":"Drug Dev. Ind. Pharm. Taylor Fr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1208\/s12249-020-01863-1","article-title":"Latanoprost Loaded in Polymeric Nanocapsules for Effective Topical Treatment of Alopecia","volume":"21","author":"Oliveira","year":"2020","journal-title":"AAPS PharmSciTech."},{"key":"ref_38","first-page":"248","article-title":"Development of a topical ointment of betamethasone dipropionate loaded nanostructured lipid carrier","volume":"11","author":"Kong","year":"2016","journal-title":"Asian J. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ejpb.2016.12.018","article-title":"Investigation of the cutaneous penetration behavior of dexamethasone loaded to nano-sized lipid particles by EPR spectroscopy, and confocal Raman and laser scanning microscopy","volume":"116","author":"Lohan","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yu, Y.Q., Yang, X., Wu, X.F., and Fa, Y.B. (2021). Enhancing Permeation of Drug Molecules Across the Skin via Delivery in Nanocarriers: Novel Strategies for Effective Transdermal Applications. Front. Bioeng. Biotechnol., 29.","DOI":"10.3389\/fbioe.2021.646554"},{"key":"ref_41","unstructured":"ICH (2023). Harmonised Tripartite Guideline. Validation of Analytical Procedures: Text and Methodology Q2 (R1), Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-q-2-r1-validation-analytical-procedures-text-methodology-step-5_en.pdf."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1007\/s11095-017-2166-7","article-title":"Polycaprolactone Based Nanoparticles Loaded with Indomethacin for Anti-Inflammatory Therapy: From Preparation to Ex Vivo Study","volume":"34","author":"Badri","year":"2017","journal-title":"Pharm. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"129941","DOI":"10.1016\/j.cej.2021.129941","article-title":"Fast and easy quantification of semi-crystalline microplastics in exemplary environmental matrices by differential scanning calorimetry (DSC)","volume":"423","author":"Bitter","year":"2021","journal-title":"J. Chem. Eng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"112136","DOI":"10.1016\/j.measurement.2022.112136","article-title":"On the latent limit of detection of thermogravimetric analysis","volume":"204","author":"Tsioptsias","year":"2022","journal-title":"Measurement"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/9\/1322\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:53:42Z","timestamp":1760129622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/9\/1322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,19]]},"references-count":44,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ph16091322"],"URL":"https:\/\/doi.org\/10.3390\/ph16091322","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,19]]}}}