{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T07:07:22Z","timestamp":1783494442575,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,22]],"date-time":"2020-11-22T00:00:00Z","timestamp":1606003200000},"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 topical administration of active compounds represents an advantageous strategy to reach the various skin components as well as its appendages. Pilosebaceous follicles are skin appendages originating in the deeper skin layers. They are very difficult to target, and hence higher active dosages are generally required to achieve effective biological responses, thus favoring the rise of side effects. The aim of this work was to design a supramolecular colloidal carrier, i.e., a liquid crystal nanocarrier, for the selective delivery of active compounds into the pilosebaceous follicle. This nanocarrier showed mean sizes of ~80 nm, a good stability, a negative surface charge, and great safety properties. In vitro studies highlighted its ability to contain and release different substances and to successfully permeate the skin. Minoxidil was encapsulated in the nanocarriers and the in vivo biological effect was compared with a conventional dosage form. Minoxidil-loaded liquid crystal nanocarrier was able to selectively reach the pilosebaceous follicle, thus allowing an increased biological effectiveness of the delivered active in terms of biological response, duration of the biological effects, and reduction of collaterals. Our investigation showed that liquid crystal nanocarriers represent a promising device for the treatment of different pilosebaceous follicular impairments\/diseases.<\/jats:p>","DOI":"10.3390\/pharmaceutics12111127","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T11:50:34Z","timestamp":1606132234000},"page":"1127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Targeting of the Pilosebaceous Follicle by Liquid Crystal Nanocarriers: In Vitro and In Vivo Effects of the Entrapped Minoxidil"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8062-817X","authenticated-orcid":false,"given":"Massimo","family":"Fresta","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, Campus Universitario \u201cS. Venuta\u201d, viale Europa, 88100 Germaneto (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0915-8643","authenticated-orcid":false,"given":"Antonia","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, Campus Universitario \u201cS. Venuta\u201d, viale Europa, 88100 Germaneto (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5510-7599","authenticated-orcid":false,"given":"Maria Chiara","family":"Cristiano","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, Campus Universitario \u201cS. Venuta\u201d, viale Europa, 88100 Germaneto (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Urbanek","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, Campus Universitario \u201cS. Venuta\u201d, viale Europa, 88100 Germaneto (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7429-5591","authenticated-orcid":false,"given":"Felisa","family":"Cilurzo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Chieti\u2014Pescara \u201cG. d\u2019Annunzio\u201d, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4898-0365","authenticated-orcid":false,"given":"Donato","family":"Cosco","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, Campus Universitario \u201cS. Venuta\u201d, viale Europa, 88100 Germaneto (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelangelo","family":"Iannone","sequence":"additional","affiliation":[{"name":"National Council of Research (CNR), The Institute for Biomedical Research and Innovation, viale Europa, 88100 Germaneto (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5223-9879","authenticated-orcid":false,"given":"Donatella","family":"Paolino","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Gr\u00e6cia\u201d of Catanzaro, Campus Universitario \u201cS. Venuta\u201d, viale Europa, 88100 Germaneto (CZ), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/17425247.2020.1713087","article-title":"Permeation enhancers in transdermal drug delivery: Benefits and limitations","volume":"17","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/bjd.17981","article-title":"Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis","volume":"181","author":"Clayton","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ejpb.2015.06.020","article-title":"Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route","volume":"97","author":"Lauterbach","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"110928","DOI":"10.1016\/j.colsurfb.2020.110928","article-title":"Stratum corneum lipid matrix with unusual packing: A molecular dynamics study","volume":"190","author":"Antunes","year":"2020","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mohd, F., Todo, H., Yoshimoto, M., Yusuf, E., and Sugibayashi, K. (2016). Contribution of the Hair Follicular Pathway to Total Skin Permeation of Topically Applied and Exposed Chemicals. Pharmaceutics, 8.","DOI":"10.3390\/pharmaceutics8040032"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1001\/archdermatol.2010.101","article-title":"Folliculotropic Mycosis Fungoides: Single-center study and systematic review","volume":"146","author":"Lehman","year":"2010","journal-title":"Arch. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.jid.2018.01.007","article-title":"Propionibacterium acnes-Derived Extracellular Vesicles Promote Acne-Like Phenotypes in Human Epidermis","volume":"138","author":"Choi","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"301","DOI":"10.2165\/00128071-200405050-00003","article-title":"Folliculitis: Recognition and management","volume":"5","author":"Santandreu","year":"2004","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.biocel.2009.11.017","article-title":"Sebocytes, multifaceted epithelial cells: Lipid production and holocrine secretion","volume":"42","author":"Schneider","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1517\/13543776.2016.1131267","article-title":"Topical drug delivery systems: A patent review","volume":"26","author":"Malik","year":"2016","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1517\/17425240903071029","article-title":"Vesicular carriers for dermal drug delivery","volume":"6","author":"Sinico","year":"2009","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1517\/17425247.5.7.737","article-title":"Colloidal carriers for the enhanced delivery through the skin","volume":"5","author":"Cosco","year":"2008","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.2174\/138945011614151119124234","article-title":"Influence of the Supramolecular Micro-Assembly of Multiple Emulsions on their Biopharmaceutical Features and In vivo Therapeutic Response","volume":"16","author":"Cilurzo","year":"2015","journal-title":"Curr. Drug Targets"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2009.04.020","article-title":"Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery","volume":"377","author":"Balakrishnan","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1038\/sj.jid.5700323","article-title":"Innovative Liposomes as a Transfollicular Drug Delivery System: Penetration into Porcine Hair Follicles","volume":"126","author":"Jung","year":"2006","journal-title":"J. Investig. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3109\/08982100903161449","article-title":"Development and characterization of minoxidil-loaded liposomal system for delivery to pilosebaceous units","volume":"20","author":"Jain","year":"2010","journal-title":"J. Liposome Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1517\/14656561003752730","article-title":"Male androgenetic alopecia","volume":"11","author":"Rathnayake","year":"2010","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bassino, E., Gasparri, F., and Munaron, L. (2020). Protective Role of Nutritional Plants Containing Flavonoids in Hair Follicle Disruption: A Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020523"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"130","DOI":"10.2174\/187221312800166859","article-title":"Minoxidil Use in Dermatology, Side Effects and Recent Patents","volume":"6","author":"Rossi","year":"2012","journal-title":"Recent Pat. Inflamm. Allergy Drug Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000096924","article-title":"Topical Use of Minoxidil in Children and Systemic Side Effects","volume":"214","author":"Georgala","year":"2007","journal-title":"Dermatology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Cristiano, M.C., Froiio, F., Spaccapelo, R., Mancuso, A., Nistic\u00f2, S.P., Udongo, B.P., Fresta, M., and Paolino, D. (2020). Sulforaphane-Loaded Ultradeformable Vesicles as A Potential Natural Nanomedicine for the Treatment of Skin Cancer Diseases. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010006"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"De Rose, R.F., Cristiano, M.C., Celano, M., Maggisano, V., Vero, A., Lombardo, G.E., Di Francesco, M., Paolino, D., Russo, D., and Cosco, D. (2016). PDE5 Inhibitors-Loaded Nanovesicles: Physico-Chemical Properties and In Vitro Antiproliferative Activity. Nanomaterials, 6.","DOI":"10.3390\/nano6050092"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Molinaro, R., Gagliardi, A., Mancuso, A., Cosco, D., Soliman, M.E., Casettari, L., and Paolino, D. (2019). Development and In Vivo Evaluation of Multidrug Ultradeformable Vesicles for the Treatment of Skin Inflammation. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120644"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ejpb.2012.02.008","article-title":"Paclitaxel-loaded ethosomes\u00ae: Potential treatment of squamous cell carcinoma, a malignant transformation of actinic keratoses","volume":"81","author":"Paolino","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1001\/archderm.1963.01590240026005","article-title":"Preparation of Isolated Sheets of Human Stratum Corneum","volume":"88","author":"Kligman","year":"1963","journal-title":"Arch. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Alexander, F.A., Eggert, S., and Wiest, J. (2018). Skin-on-a-Chip: Transepithelial Electrical Resistance and Extracellular Acidification Measurements through an Automated Air-Liquid Interface. Genes, 9.","DOI":"10.3390\/genes9020114"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0168-3659(98)00087-X","article-title":"Application of vesicles to rat skin in vivo: A confocal laser scanning microscopy study","volume":"56","author":"Mougin","year":"1998","journal-title":"J. Control. Release"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1111\/j.0022-202X.2005.23779.x","article-title":"Differential Stripping: Determination of the Amount of Topically Applied Substances Penetrated into the Hair Follicles","volume":"125","author":"Teichmann","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s13346-017-0469-1","article-title":"Nano-formulation for topical treatment of precancerous lesions: Skin penetration, in vitro, and in vivo toxicological evaluation","volume":"8","author":"Calienni","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/1523-1747.ep12355026","article-title":"Effect of Hair Growth Cycles on Experimental Cutaneous Candidiasis in Mice","volume":"86","author":"Sohnle","year":"1986","journal-title":"J. Investig. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1126\/science.2218498","article-title":"Protection from chemotherapy-induced alopecia in a rat model","volume":"249","author":"Hussein","year":"1990","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3109\/10611860108995632","article-title":"Effect of Positively and Negatively Charged Liposomes on Skin Permeation of Drugs","volume":"9","author":"Ogiso","year":"2001","journal-title":"J. Drug Target."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ijpharm.2011.03.049","article-title":"Liposome surface charge influence on skin penetration behaviour","volume":"411","author":"Gillet","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0378-5173(03)00183-2","article-title":"Particle size of liposomes influences dermal delivery of substances into skin","volume":"258","author":"Verma","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.colsurfb.2011.03.035","article-title":"Preparation, characterization and biocompatibility studies on risperidone-loaded solid lipid nanoparticles (SLN): High pressure homogenization versus ultrasound","volume":"86","author":"Silva","year":"2011","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1023\/B:PHAM.0000045235.86197.ef","article-title":"Enhancement of Topical Delivery from Biodegradable Nanoparticles","volume":"21","author":"Naik","year":"2004","journal-title":"Pharm. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"444","DOI":"10.2174\/1567201816666190201143457","article-title":"Topical and Transdermal Drug Delivery: From Simple Potions to Smart Technologies","volume":"16","author":"Benson","year":"2019","journal-title":"Curr. Drug Deliv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.4103\/2230-973X.133047","article-title":"Development and evaluation of solid lipid nanoparticles of mometasone furoate for topical delivery","volume":"4","author":"Madan","year":"2014","journal-title":"Int. J. Pharm. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1080\/14712598.2018.1430762","article-title":"Combining cell and gene therapy to advance cardiac regeneration","volume":"18","author":"Marotta","year":"2018","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.ijpharm.2013.07.031","article-title":"Nano-transfersomes as a novel carrier for transdermal delivery","volume":"454","author":"Chaudhary","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.tiv.2014.09.007","article-title":"Suitability of skin integrity tests for dermal absorption studies in vitro","volume":"29","author":"Guth","year":"2015","journal-title":"Toxicol. In Vitro"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ijpharm.2004.12.022","article-title":"Non-invasive vaccine delivery in transfersomes, niosomes and liposomes: A comparative study","volume":"293","author":"Gupta","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_43","first-page":"4214","article-title":"A Comparison Study of Liposomes, Transfersomes and Ethosomes Bearing Lamivudine","volume":"7","author":"Sudhakar","year":"2016","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1517\/17425247.3.6.727","article-title":"Transfersomes for transdermal drug delivery","volume":"3","author":"Benson","year":"2006","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1325708","DOI":"10.1080\/20022727.2017.1325708","article-title":"Transfersomes as versatile and flexible nano-vesicular carriers in skin cancer therapy: The state of the art","volume":"8","author":"Rai","year":"2017","journal-title":"Nano Rev. Exp."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2017.10.046","article-title":"Lipid nanocarriers as skin drug delivery systems: Properties, mechanisms of skin interactions and medical applications","volume":"535","author":"Sala","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_47","first-page":"482","article-title":"Acronychiabaueri Analogue Derivative-Loaded Ultradeformable Vesicles: Physicochemical Characterization and Potential Applications","volume":"83","author":"Primavera","year":"2017","journal-title":"Planta Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/0005-2736(92)90154-E","article-title":"Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force","volume":"1104","author":"Cevc","year":"1992","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1046\/j.1365-2133.1997.d01-1156.x","article-title":"Diffuse hypertrichosis during treatment with 5% topical minoxidil","volume":"136","author":"Peluso","year":"1997","journal-title":"Br. J. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"R132","DOI":"10.1016\/j.cub.2008.12.005","article-title":"The Hair Follicle as a Dynamic Miniorgan","volume":"19","author":"Schneider","year":"2009","journal-title":"Curr. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/j.1524-6175.2004.03585.x","article-title":"Minoxidil: An underused vasodilator for resistant or severe hypertension","volume":"6","author":"Sica","year":"2004","journal-title":"J. Clin. Hypertens."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.ijpharm.2014.11.072","article-title":"Glycerol monooleate liquid crystalline phases used in drug delivery systems","volume":"478","author":"Milak","year":"2015","journal-title":"Int. J. Pharm."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/11\/1127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:35:43Z","timestamp":1760178943000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/11\/1127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,22]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["pharmaceutics12111127"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12111127","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,22]]}}}