{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:10:10Z","timestamp":1785867010709,"version":"3.56.0"},"reference-count":95,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T00:00:00Z","timestamp":1599782400000},"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>Sodium valproate (SV) is an antiepileptic drug that is widely used in the treatment of different seizure disorders. The topical SV has a hair regenerative potential through activating the Wnt\/\u03b2-catenin pathway and anagen phase induction. The aim of the current investigation was to fabricate nanospanlastics of SV for improving its dermal delivery by providing prolonged drug effect and increasing its permeability for treatment of androgenic alopecia (AGA). SV-loaded nanospanlastics were formulated according to 23 factorial design by ethanol injection method using a non-ionic surfactant (Span 60) and edge activators (EAs), such as Tween 80 and Cremophor RH 40, to explore the influence of different independent variables on entrapment efficiency (EE%) and percentage drug released after 12 h (Q12h) in order to choose the optimized formula using Design-Expert software. The optimized formula (F8) appeared as spherical deformable vesicles with EE% of 90.32 \u00b1 2.18% and Q12h of 90.27 \u00b1 1.98%. F8 exhibited significant improvement of ex vivo permeation than free SV. The clinical study exhibited no comparable difference between F8 and marketed minoxidil lotion. However, F8 demonstrates less adverse effects than minoxidil lotion. Nanospanlastics could be a safe and effective method for improving the topical delivery of SV in the management of AGA.<\/jats:p>","DOI":"10.3390\/pharmaceutics12090866","type":"journal-article","created":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T09:05:16Z","timestamp":1599815116000},"page":"866","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Formulation of Sodium Valproate Nanospanlastics as a Promising Approach for Drug Repurposing in the Treatment of Androgenic Alopecia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7230-3105","authenticated-orcid":false,"given":"Farid. A.","family":"Badria","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan A.","family":"Fayed","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, Mansoura University, Mansoura 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira K.","family":"Ibraheem","sequence":"additional","affiliation":[{"name":"Mansoura Dermatology and Leprosy Hospital, Mansoura 35511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed F.","family":"State","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, Mansoura University, Mansoura 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman A.","family":"Mazyed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zarkesh, K., Khazaeli, P., Pardakhty, A., and Rezaifar, M. (2016). Preparation and Physicochemical Characterization of Topical Niosomal Formulation of Minoxidil and Tretinoin, School of Pharmacy, Kerman University of Medical Sciences.","DOI":"10.19080\/GJPPS.2017.03.555606"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"126","DOI":"10.4103\/0974-7753.125606","article-title":"Application of the basic and specific classification on patterned hair loss in Indians","volume":"5","author":"Agarwal","year":"2013","journal-title":"Int. J. Trichol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4103\/ijt.ijt_89_18","article-title":"Comparative study between mesotherapy and topical 5% minoxidil by dermoscopic evaluation for androgenic alopecia in male: A randomized controlled trial","volume":"11","author":"Gajjar","year":"2019","journal-title":"Int. J. Trichol."},{"key":"ref_4","first-page":"541","article-title":"Female pattern alopecia: Current perspectives","volume":"5","author":"Levy","year":"2013","journal-title":"Int. J. Women\u2019s Health"},{"key":"ref_5","unstructured":"Egbuna, C., Kumar, S., Ifemeje, J.C., Ezzat, S.M., and Kaliyaperumal, S. (2019). Phytochemicals as Lead Compounds for New Drug Discovery, Elsevier."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4103\/2229-5178.148925","article-title":"Topical minoxidil fortified with finasteride: An account of maintenance of hair density after replacing oral finasteride","volume":"6","author":"Chandrashekar","year":"2015","journal-title":"Indian Dermatol. Online J."},{"key":"ref_7","first-page":"14","article-title":"Topical Valproate Solution for Hair Growth","volume":"17","author":"Kakunje","year":"2018","journal-title":"Online J. Health Allied Sci."},{"key":"ref_8","first-page":"1132","article-title":"Tolerance to and unwanted effects of valproate sodium","volume":"83","author":"Despland","year":"1994","journal-title":"Praxis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.1002\/app.35527","article-title":"Valproate-Loaded hydrogel nanoparticles: Preparation and characterization","volume":"124","author":"Hamidi","year":"2012","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lee, S.-H., Yoon, J., Shin, S.H., Zahoor, M., Kim, H.J., Park, P.J., Park, W.-S., Min, D.S., Kim, H.-Y., and Choi, K.-Y. (2012). Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034152"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/1346-8138.12422","article-title":"Topical valproic acid increases the hair count in male patients with androgenetic alopecia: A randomized, comparative, clinical feasibility study using phototrichogram analysis","volume":"41","author":"Jo","year":"2014","journal-title":"J. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e214","DOI":"10.1111\/j.1365-4632.2012.05832.x","article-title":"A case of androgenetic alopecia treated with valproic acid","volume":"53","author":"Choi","year":"2014","journal-title":"Int. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jddst.2017.12.003","article-title":"Formulation and optimization of transfersome containing minoxidil and caffeine","volume":"44","author":"Ramezani","year":"2018","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1208\/s12249-017-0771-8","article-title":"Topical delivery of fenoprofen calcium via elastic nano-vesicular spanlastics: Optimization using experimental design and in vivo evaluation","volume":"18","author":"Farghaly","year":"2017","journal-title":"AAPS PharmSciTech"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ijpharm.2010.06.034","article-title":"Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery","volume":"397","author":"Awad","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ijpharm.2017.03.005","article-title":"Enhanced non invasive trans-tympanic delivery of ciprofloxacin through encapsulation into nano-spanlastic vesicles: Fabrication, in-vitro characterization, and comparative ex-vivo permeation studies","volume":"522","author":"Khowessah","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_17","unstructured":"US Food and Drug Administration (2012). Database of Select Committee on GRAS Substances (SCOGS) Reviews."},{"key":"ref_18","unstructured":"US Food and Drug Administration (2017). Inactive Ingredient Search for Approved Drug Products."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1039\/C4MD00085D","article-title":"Amphiphilic designer nano-carriers for controlled release: From drug delivery to diagnostics","volume":"5","author":"Salim","year":"2014","journal-title":"MedChemComm"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1080\/10717544.2016.1247928","article-title":"Ocular ketoconazole-loaded proniosomal gels: Formulation, ex vivo corneal permeation and in vivo studies","volume":"24","author":"Abdelbary","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/10717544.2017.1410262","article-title":"Penetration enhancer-containing spanlastics (PECSs) for transdermal delivery of haloperidol: In vitro characterization, ex vivo permeation and in vivo biodistribution studies","volume":"25","author":"Fahmy","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"855","DOI":"10.3109\/03639045.2010.546404","article-title":"Optimization of acyclovir oral tablets based on gastroretention technology: Factorial design analysis and physicochemical characterization studies","volume":"37","author":"Naggar","year":"2011","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3109\/08982100903347923","article-title":"Ethanol injection method for hydrophilic and lipophilic drug-loaded liposome preparation","volume":"20","author":"Diab","year":"2010","journal-title":"J. Liposome Res."},{"key":"ref_24","unstructured":"Larsson, J. (2009). Methods for Measurement of Solubility and Dissolution Rate of Sparingly Soluble Drugs. [Master\u2019s Thesis, Lund University]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.2147\/DDDT.S144652","article-title":"A novel transdermal nanoethosomal gel of betahistine dihydrochloride for weight gain control: In-vitro and in-vivo characterization","volume":"11","author":"Ali","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_26","first-page":"1143","article-title":"Kinetic analysis of in vitro drug release from valproic acid and sodium valproate suppositories","volume":"62","author":"Ciurba","year":"2014","journal-title":"Farmacia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.5530\/ijper.47.3.6","article-title":"Development of valproic acid niosomal in situ nasal gel formulation for epilepsy","volume":"16","author":"Chaudhari","year":"2013","journal-title":"Indian J. Pharm. Educ. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kumar, P., Singh, S.K., Handa, V., and Kathuria, H. (2018). Oleic acid nanovesicles of minoxidil for enhanced follicular delivery. Medicines, 5.","DOI":"10.3390\/medicines5030103"},{"key":"ref_29","unstructured":"Koehler, K.R. (1996). Body Temperature Regulation, University of Cincinnati Raymond Walters College."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.1080\/10717544.2016.1183721","article-title":"Trans-nasal zolmitriptan novasomes: In-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency","volume":"23","author":"Shamma","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mazyed, E.A., and Abdelaziz, A.E. (2020). Fabrication of Transgelosomes for Enhancing the Ocular Delivery of Acetazolamide: Statistical Optimization, In Vitro Characterization, and In Vivo Study. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12050465"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"318","DOI":"10.4103\/0975-7406.120080","article-title":"Design and development of cefdinir niosomes for oral delivery","volume":"5","author":"Bansal","year":"2013","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.22159\/ijap.2019v11i2.30575","article-title":"Enhancement of dissolution characteristics of clopidogrel bisulphate by proniosomes","volume":"11","author":"Mazyed","year":"2019","journal-title":"Int. J. Appl. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"687","DOI":"10.4314\/tjpr.v6i2.14647","article-title":"Design and development of a proniosomal transdermal drug delivery system for captopril","volume":"6","author":"Gupta","year":"2007","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.ijpharm.2014.06.041","article-title":"Nano-transfersomal ciprofloxacin loaded vesicles for non-invasive trans-tympanic ototopical delivery: In-vitro optimization, ex-vivo permeation studies, and in-vivo assessment","volume":"472","author":"Khowessah","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s13346-012-0083-1","article-title":"Niosomes as a vesicular carrier for topical administration of minoxidil: Formulation and in vitro assessment","volume":"3","author":"Mali","year":"2013","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0140-6736(86)92571-7","article-title":"The Animals (scientific procedures) Act 1986","volume":"2","author":"Hollands","year":"1986","journal-title":"Lancet"},{"key":"ref_38","first-page":"33","article-title":"63\/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes","volume":"276","author":"Directive","year":"2010","journal-title":"Off. J. Eur. Union"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kilkenny, C., Browne, W.J., Cuthill, I.C., Emerson, M., and Altman, D.G. (2010). Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000412"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.2147\/DDDT.S171888","article-title":"Finasteride nano-transferosomal gel formula for management of androgenetic alopecia: Ex vivo investigational approach","volume":"12","author":"Ahmed","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1211\/jpp.62.02.0016","article-title":"3-Acetyl-11-keto-\u03b2-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity","volume":"62","author":"Goel","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lemaire, F.J. (2003). A European Directive for Clinical Research, Springer.","DOI":"10.1007\/s00134-003-1963-0"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"World Medical Association (2001). World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bull. World Health Organ., 79, 373.","DOI":"10.4414\/smf.2001.04031"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1111\/j.1749-6632.1951.tb31971.x","article-title":"Patterned loss of hair in man: Types and incidence","volume":"53","author":"Hamilton","year":"1951","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1365-2133.1977.tb15179.x","article-title":"Classification of the types of androgenetic alopecia (common baldness) occurring in the female sex","volume":"97","author":"Ludwig","year":"1977","journal-title":"Br. J. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4055\/cios.2014.6.1.103","article-title":"How to do random allocation (randomization)","volume":"6","author":"Kim","year":"2014","journal-title":"Clin. Orthop. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4103\/0250-474X.65026","article-title":"Preparation of coated valproic acid and sodium valproate sustained-release matrix tablets","volume":"72","author":"Phaechamud","year":"2010","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_48","unstructured":"ICH, I. (2005, January 8\u201313). Q2 (R1): Validation of analytical procedures: Text and methodology. Proceedings of the International Conference on Harmonization, Geneva, Switzerland."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.fitote.2012.06.006","article-title":"Development of an isocratic HPLC method for catechin quantification and its application to formulation studies","volume":"83","author":"Li","year":"2012","journal-title":"Fitoterapia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1208\/s12249-008-9105-1","article-title":"Niosome-encapsulated gentamicin for ophthalmic controlled delivery","volume":"9","author":"Abdelbary","year":"2008","journal-title":"AAPS PharmSciTech"},{"key":"ref_51","first-page":"221","article-title":"Formulation and evaluation of propranolol hydrochloride-loaded carbopol-934p\/ethyl cellulose mucoadhesive microspheres","volume":"9","author":"Patel","year":"2010","journal-title":"IJPR"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ijpharm.2010.03.034","article-title":"Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications","volume":"393","author":"Araujo","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1208\/s12249-013-0048-9","article-title":"Formulation and optimization of nonionic surfactants emulsified nimesulide-loaded PLGA-based nanoparticles by design of experiments","volume":"15","author":"Turk","year":"2014","journal-title":"AAPS PharmSciTech"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jss.2007.02.053","article-title":"Analysis of variance: Is there a difference in means and what does it mean?","volume":"144","author":"Kao","year":"2008","journal-title":"J. Surg. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.ijpharm.2017.11.023","article-title":"Novel cremochylomicrons for improved oral bioavailability of the antineoplastic phytomedicine berberine chloride: Optimization and pharmacokinetics","volume":"535","author":"Elsheikh","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_56","first-page":"864","article-title":"Effect of alginate and surfactant on physical properties of oil entrapped alginate bead formulation of curcumin","volume":"7","author":"Petchsomrit","year":"2013","journal-title":"Int. J. Med. Health Biomed Bioeng Pharm. Eng."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ejpb.2010.07.011","article-title":"Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats","volume":"76","author":"Setthacheewakul","year":"2010","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"274","DOI":"10.4103\/0250-474X.33156","article-title":"A comparative solubility enhancement profile of valdecoxib with different solubilization approaches","volume":"69","author":"Modi","year":"2007","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S2221-1691(12)60241-X","article-title":"Preparation and characterization of curcumin\u2013piperine dual drug loaded nanoparticles","volume":"2","author":"Moorthi","year":"2012","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ijpharm.2010.03.008","article-title":"SNEDDS containing bioenhancers for improvement of dissolution and oral absorption of lacidipine. I: Development and optimization","volume":"391","author":"Basalious","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_61","first-page":"305","article-title":"Application of desirability function for optimizing the performance characteristics of carbonitrided bushes","volume":"4","author":"John","year":"2013","journal-title":"Int. J. Ind. Eng. Comput."},{"key":"ref_62","first-page":"438","article-title":"Sorbitan ester niosomes for topical delivery of rofecoxib","volume":"49","author":"Das","year":"2011","journal-title":"Indian J. Exp. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0099-5428(05)32008-9","article-title":"Valproic acid and sodium valproate: Comprehensive profile","volume":"32","author":"Alsarra","year":"2005","journal-title":"Profiles Drug Subst. Excip. Relat. Methodol."},{"key":"ref_64","first-page":"1377","article-title":"Solid-state forms of sodium valproate, active component of the anticonvulsant drug epilim","volume":"3","author":"Naumov","year":"2008","journal-title":"ChemMedChem Chem. Enabling Drug Discov."},{"key":"ref_65","first-page":"127","article-title":"Preparation and evaluation of rapidly dissolving tablets of raloxifene hydrochloride by ternary system formation","volume":"8","author":"Ghanem","year":"2016","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1080\/03639045.2016.1272120","article-title":"Flurbiprofen-loaded niosomes-in-gel system improves the ocular bioavailability of flurbiprofen in the aqueous humor","volume":"43","author":"Hussein","year":"2017","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_67","first-page":"2446","article-title":"Formulation and evaluation of Sodium Valproate Sustained Released Tablets","volume":"6","author":"Srikrishna","year":"2015","journal-title":"J. Glob. Trends Pharm. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"731","DOI":"10.3109\/10717544.2014.896428","article-title":"Formulation of tretinoin-loaded topical proniosomes for treatment of acne: In-vitro characterization, skin irritation test and comparative clinical study","volume":"22","author":"Rahman","year":"2015","journal-title":"Drug Deliv."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Yeo, L., Olusanya, T., Chaw, C., and Elkordy, A. (2018). Brief effect of a small hydrophobic drug (cinnarizine) on the physicochemical characterisation of Niosomes produced by thin-film hydration and microfluidic methods. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10040185"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3109\/10837450.2012.685655","article-title":"A novel nanovesicular carrier system to deliver drug topically","volume":"18","author":"Kakkar","year":"2013","journal-title":"Pharm. Dev. Technol."},{"key":"ref_71","first-page":"517","article-title":"Formulation and evaluation of maltodextrin based proniosomes loaded with indomethacin","volume":"1","author":"Sengodan","year":"2009","journal-title":"Int. J. PharmTech Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3109\/08982104.2013.788025","article-title":"Design and optimization of surfactant-based nanovesicles for ocular delivery of Clotrimazole","volume":"23","author":"Basha","year":"2013","journal-title":"J. Liposome Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.cplett.2008.07.094","article-title":"Effect of hydration on the structure of solid-supported Niosomal membranes investigated by in situ energy dispersive X-ray diffraction","volume":"462","author":"Caracciolo","year":"2008","journal-title":"Chem. Phys. Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1208\/s12249-008-9121-1","article-title":"Effect of charged and non-ionic membrane additives on physicochemical properties and stability of niosomes","volume":"9","author":"Junyaprasert","year":"2008","journal-title":"AAPS PharmSciTech"},{"key":"ref_75","first-page":"227","article-title":"Effect of formulation and processing variables on the particle size of sorbitan monopalmitate niosomes","volume":"4","author":"Essa","year":"2014","journal-title":"Asian J. Pharm. (AJP) Free Full Text Artic. Asian J. Pharm."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2174\/1874844901603010031","article-title":"Optimization of Bifonazole-Loaded Nisomal Formulation Using Plackett-Burman Design and 23 Factorial Design","volume":"3","author":"Pawar","year":"2016","journal-title":"Open Pharm. Sci. J."},{"key":"ref_77","first-page":"193","article-title":"Nanoparticles for dermal and transdermal drug delivery","volume":"4","author":"Uchechi","year":"2014","journal-title":"Appl. Nanotechnol. Drug Deliv."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1208\/s12249-016-0489-z","article-title":"Systematic development of transethosomal gel system of piroxicam: Formulation optimization, in vitro evaluation, and ex vivo assessment","volume":"18","author":"Garg","year":"2017","journal-title":"AAPS PharmSciTech"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.ijpharm.2008.04.033","article-title":"Anti-inflammatory activity of gel containing novel elastic niosomes entrapped with diclofenac diethylammonium","volume":"360","author":"Manosroi","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"329","DOI":"10.22159\/ijap.2019v11i5.33615","article-title":"Optimization of sodium deoxycholate-based transfersomes for percutaneous delivery of peptides and proteins","volume":"11","author":"Leonyza","year":"2019","journal-title":"Int. J. Appl. Pharm."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Zsik\u00f3, S., Cs\u00e1nyi, E., Kov\u00e1cs, A., Budai-Sz\u0171cs, M., G\u00e1csi, A., and Berk\u00f3, S. (2019). Methods to evaluate skin penetration In Vitro. Sci. Pharm., 87.","DOI":"10.3390\/scipharm87030019"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ejps.2015.02.018","article-title":"In vitro skin models as a tool in optimization of drug formulation","volume":"75","author":"Flaten","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Todo, H. (2017). Transdermal permeation of drugs in various animal species. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9030033"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0378-5173(92)90089-K","article-title":"Prediction of skin permeability of drugs. II. Development of composite membrane as a skin alternative","volume":"79","author":"Tomomi","year":"1992","journal-title":"Int. J. Pharm."},{"key":"ref_85","first-page":"1","article-title":"Utility of three-dimensional cultured human skin model as a tool to evaluate skin permeation of drugs","volume":"8","author":"Watanabe","year":"2001","journal-title":"Altern. Anim. Test. Exp."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1538\/expanim.60.373","article-title":"Usefulness of rat skin as a substitute for human skin in the in vitro skin permeation study","volume":"60","author":"Takeuchi","year":"2011","journal-title":"Exp. Anim."},{"key":"ref_87","first-page":"163","article-title":"Skin models for the testing of transdermal drugs","volume":"8","author":"Abd","year":"2016","journal-title":"Clin. Pharmacol. Adv. Appl."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/j.addr.2007.07.004","article-title":"Transdermal skin delivery: Predictions for humans from in vivo, ex vivo and animal models","volume":"59","author":"Godin","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3109\/08982104.2012.700460","article-title":"Brain delivery of olanzapine by intranasal administration of transfersomal vesicles","volume":"22","author":"Salama","year":"2012","journal-title":"J. Liposome Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.2174\/1567201815666180619105419","article-title":"Implementing Central Composite Design for Developing Transdermal Diacerein-Loaded Niosomes: Ex vivo Permeation and In vivo Deposition","volume":"15","author":"Aziz","year":"2018","journal-title":"Curr. Drug Deliv."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jaad.2008.03.031","article-title":"The role of scalp dermoscopy in the diagnosis of alopecia areata incognita","volume":"59","author":"Tosti","year":"2008","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0190-9622(99)70006-X","article-title":"Changes in hair weight and hair count in men with androgenetic alopecia, after application of 5% and 2% topical minoxidil, placebo, or no treatment","volume":"41","author":"Price","year":"1999","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"90","DOI":"10.18311\/mvpjms\/2015\/v2\/i2\/781","article-title":"Comparative Study of Efficacy of Topical Minoxidil 5% and Combination of Topical Minoxidil 5%, Topical Azelaic Acid 1.5% and Topical Tretinoin 0.01% on the Basis of Dermoscopic Analysis in Androgenetic Alopecia","volume":"2","author":"Gugle","year":"2015","journal-title":"MVP J. Med Sci."},{"key":"ref_94","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_95","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1067\/mjd.2001.117428","article-title":"Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss","volume":"45","author":"Whiting","year":"2001","journal-title":"J. Am. Acad. Dermatol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/9\/866\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:09:12Z","timestamp":1760177352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/9\/866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,11]]},"references-count":95,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["pharmaceutics12090866"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12090866","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,11]]}}}