Background/Aims: Androgenetic alopecia is an extremely common dermatological disorder affecting both men and women. Oral finasteride (FNS), a synthetic 4-aza-3-oxosteroid compound with poor aqueous solubility, blocks the peripheral conversion of testosterone to dihydrotestosterone (DHT) in a significant reduction in DHT concentration, achieving satisfactory results in alopecia treatment. However, its oral intake generally causes severe side effects. Considering that there is currently no scientifically proven treatment, new drug delivery systems able to improve alopecia therapy are urgently required. Methods: In this study, polymeric nanoparticles have been proposed as a new carrier for topical delivery of FNS in hair follicles. Results and Conclusions: Polymeric nanoparticles, prepared by using a modified method of the emulsification/solvent diffusion, showed a mean particle size around 300 nm, which may be sufficient for reaching the dermis and hair follicles and negative zeta potential values. Scanning electron microscope measurements showed that all the polymeric nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. A high encapsulation efficiency was achieved for FNS (79.49 ± 0.47%). In vitro release assays in physiological conditions demonstrated that nanoparticles yielded a prolonged release of FNS for 3 h. Skin assays through an in vitro permeation study demonstrated that nanoparticles had low levels of penetration of FNS, improving its time residence onto the skin. All excipients used in nanoparticle composition and in 3 different vehicles were safe. These results suggest that the proposed novel formulation presents several good characteristics indicating its suitability for dermal delivery of FNS for alopecia treatment.

1.
Sato A, Takeda A: Evaluation of efficacy and safety of finasteride 1 mg in 3,177 Japanese men with androgenetic alopecia. J Dermatol 2012;39:27-32.
2.
Kumar R, Singh B, Bakshi G, Katare OP: Development of liposomal systems of finasteride for topical applications: design, characterization, and in vitro evaluation. Pharm Dev Technol 2007;12:591-601.
3.
Libecco JF, Bergfeld WF: Finasteride in the treatment of alopecia. Expert Opin Pharmacother 2004;5:933-940.
4.
Lademann J, Richter H, Teichmann A, Otberg N, Blume-Peytavi U, Luengo J, Weiss B, Schaefer UF, Lehr C-M, Wepf R: Nanoparticles - an efficient carrier for drug delivery into the hair follicles. Eur J Pharm Biopharm 2007;66:159-164.
5.
Ahlin Grabnar P, Kristl J: The manufacturing techniques of drug-loaded polymeric nanoparticles from preformed polymers. J Microencapsul 2011;28:323-335.
6.
Couvreur P, Barratt G, Fattal E, Legrand P, Vauthier C: Nanocapsule technology: a review. Crit Rev Ther Drug Carrier Syst 2002;19:99-134.
7.
Reis CP, Roque LV, Baptista M, Rijo P: Innovative formulation of nystatin particulate systems in toothpaste for candidiasis treatment. Pharm Dev Technol 2016;21:282-287.
8.
Madheswaran T, Baskaran R, Thapa RK, Rhyu JY, Choi HY, Kim JO, Yong CS, Yoo BK: Design and in vitro evaluation of finasteride-loaded liquid crystalline nanoparticles for topical delivery. AAPS PharmSciTech 2013;14:45-52.
9.
Song SY: Future direction of nanomedicine in gastrointestinal cancer. Korean J Gastroenterol 2007;49:271-279.
10.
Tanaka T, Decuzzi P, Cristofanilli M, Sakamoto JH, Tasciotti E, Robertson FM, Ferrari M: Nanotechnology for breast cancer therapy. Biomed Microdevices 2009;11:49-63.
11.
Zhang H, Cui W, Bei J, Wang S: Preparation of poly(lactide-co-glycolide-co-caprolactone) nanoparticles and their degradation behaviour in aqueous solution. Polym Degrad Stab 2006;91:1929-1936.
12.
Martinho N, Rosado C, Reis CP: Influência de duas técnicas diferentes no tamanho e potencial zeta de nanopartículas de poli (DL-láctico-co-glicólico). Rev Lusófona Ciências Tecnol Saúde 2011;8:329-338.
13.
Jana U, Mohanty AK, Pal SL, Manna PK, Mohanta GP: Felodipine loaded PLGA nanoparticles: preparation, physicochemical characterization and in vivo toxicity study. Nano Converg 2014;1:31.
14.
Peng D, Huang K, Liu Y, Liu S: Preparation of novel polymeric microspheres for controlled release of finasteride. Int J Pharm 2007;342:82-86.
15.
Rowe RC, Sheskey PJ, Quinn ME (eds): Handbook of Pharmaceutical Excipients, ed 6. London, The Pharmaceutical Press, 2010, pp 637-638.
16.
Trüeb RM: The value of hair cosmetics and pharmaceuticals. Dermatology 2001;202:275-282.
17.
Noudeh GD, et al: Formulation of herbal conditioner shampoo by using extract of fenugreek seeds and evaluation of its physicochemical parameters. African J Pharm Pharmacol 2011;5:2420-2427.
18.
Moldovan M, Părăuan S: Cosmetic evaluation of some commercial shampoos. Farm Clujul Med 2012;85:378-383.
19.
Esmaeili F, Atyabi F, Dinarvand R: Preparation of PLGA nanoparticles using TPGS in the spontaneous emulsification solvent diffusion method. J Exp Nanosci 2007;2:183-192.
20.
Murakami H, Kobayashi M, Takeuchi H, Kawashima Y: Further application of a modified spontaneous emulsification solvent diffusion method to various types of PLGA and PLA polymers for preparation of nanoparticles. Powder Technol 2000;107:137-143.
21.
Murakami H, Kobayashi M, Takeuchi H, Kawashima Y: Preparation of poly(dl-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method. Int J Pharm 1999;187:143-152.
22.
Gomes A, Ascensão L, Rijo P, Baptista M, Candeias S, Martinho N, Fernandes A, Roberto A, Reis C: Evaluation of a new topical treatment for acne with azelaic acid-loaded nanoparticles. Microsc Microanal 2013;19:59-60.
23.
van Tonder A, Joubert AM, Cromarty A: Limitations of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay when compared to three commonly used cell enumeration assays. BMC Res Notes 2015;8:47.
24.
Chauhan D, Ray A, Viktorsson K, Spira J, Paba-Prada C, Munshi N, Richardson P, Lewensohn R, Anderson KC: In vitro and in vivo antitumor activity of a novel alkylating agent, melphalan-flufenamide, against multiple myeloma cells. Clin Cancer Res 2013;19:3019-3031.
25.
Roberto A, Caetano P: A high-throughput screening method for general cytotoxicity. Part I: chemical toxicity. Rev Lusófona Ciências Tecnol Saúde 2005;2:95-100.
26.
Marrot L, Labarussiat A, Perez P, Meunier JR: Use of the yeast Saccharomyces cerevisiae as a pre-screening approach for assessment of chemical-induced phototoxicity. Toxicol Vitr 2006;20:1040-1050.
27.
Holder AL, Goth-Goldstein R, Lucas D, Koshland CP: Particle-induced artifacts in the MTT and LDH viability assays. Chem Res Toxicol 2012;25:1885-1892.
28.
Löffler H, Happle R: Influence of climatic conditions on the irritant patch test with sodium lauryl sulphate. Acta Derm Venereol 2003;83:338-341.
29.
Flannigan SA, Smith RE, McGovern JP: Intraregional variation between contact Irritant patch test sites. Contact Dermatitis 1984;10:123-124.
30.
York M, Griffiths HA, Whittle E, Basketter DA: Evaluation of a human patch test for the identification and classification of skin irritation potential. Contact Dermatitis 1996;34:204-212.
31.
Basketter DA, York M, McFadden JP, Robinson MK: Determination of skin irritation potential in the human 4-h patch test. Contact Dermatitis 2004;51:1-4.
32.
Hemminki A: Harmful impact of EU clinical trials directive. BMJ 2006;332:501-502.
33.
Pich J, Carné X, Arnaiz J-A, Gómez B, Trilla A, Rodés J: Role of a research ethics committee in follow-up and publication of results. Lancet 2003;361:1015-1016.
34.
Feng S-S: Nanoparticles of biodegradable polymers for new-concept chemotherapy. Expert Rev Med Devices 2004;1:115-125.
35.
Vogt A, Rancan F, Ahlberg S, Nazemi B, Choe CS, Darvin ME, Hadam S, Blume-Peytavi U, Loza K, Diendorf J, Epple M, Graf C, Rühl E, Meinke MC, Lademann J: Interaction of dermatologically relevant nanoparticles with skin cells and skin. Beilstein J Nanotechnol 2014;5:2363-2373.
36.
Idson B: Adsorption to skin and hair. J Soc Cosmet Chem 1967;103:91-103.
37.
Dragicevic N, Maibach HI: Percutaneous penetration enhancers chemical methods in penetration enhancement; in: Modification of the Stratum Corneum. Berlin, Springer, 2016, pp 1-411.
38.
Yilmaz E, Borchert HH: Design of a phytosphingosine-containing, positively-charged nanoemulsion as a colloidal carrier system for dermal application of ceramides. Eur J Pharm Biopharm 2005;60:91-98.
39.
Hoeller S, Sperger A, Valenta C: Lecithin based nanoemulsions: a comparative study of the influence of non-ionic surfactants and the cationic phytosphingosine on physicochemical behaviour and skin permeation. Int J Pharm 2009;370:181-186.
40.
Silva LAD, Taveira SF, Lima EM, Marreto RN: In vitro skin penetration of clobetasol from lipid nanoparticles: drug extraction and quantitation in different skin layers. Braz J Pharm Sci 2012;48:811-817.
41.
Yang R, Shim W-S, Cui F-D, Cheng G, Han X, Jin Q-R, Kim D-D, Chung S-J, Shim C-K: Enhanced electrostatic interaction between chitosan-modified PLGA nanoparticle and tumor. Int J Pharm 2009;371:142-147.
42.
Dinarvand R, Sepehri N, Manoochehri S, Rouhani H, Atyabi F: Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents. Int J Nanomedicine 2011;6:877-895.
43.
Hubbard AT: Surfactants in Personal Care Products and Decorative Cosmetics: Angewandte Chemie International Edition. Abingdon, Routledge Taylor & Francis Group, 2006, vol 40, p 9823.
44.
Lambers H, Piessens S, Bloem A, Pronk H, Finkel P: Natural skin surface pH is on average below 5, which is beneficial for its resident flora. Int J Cosmet Sci 2006;28:359-370.
45.
Morykwas MJ, Thornton JW, Bartlett RH: Zeta potential of synthetic and biological skin substitutes: effects on initial adherence. Plast Reconstr Surg 1987;79:732-739.
46.
Parra A, Clares B, Rosselló A, Garduño-Ramírez ML, Abrego G, García ML, Calpena AC: Ex vivo permeation of carprofen from nanoparticles: a comprehensive study through human, porcine and bovine skin as anti-inflammatory agent. Int J Pharm 2016;501:10-17.
47.
Pfaller MA, Diekema DJ: Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 2007;20:133-163.
48.
Silva CO, Rijo P, Molpeceres J, Figueiredo IV, Ascensão L, Fernandes AS, Roberto A, Reis CP: Polymeric nanoparticles modified with fatty acids encapsulating betamethasone for anti-inflammatory treatment. Int J Pharm 2015;493:271-284.
49.
Lobner D: Comparison of the LDH and MTT assays for quantifying cell death: validity for neuronal apoptosis? J Neurosci Methods 2000;96:147-152.
50.
Tupker RA, Willis C, Berardksca E, Lee CH, Fartasch M, Atinrat T, Serup J: Guidelines on sodium lauryl sulfate (SLS) exposure tests. Contact Dermatitis 1997;37:53-69.
51.
Fullerton A, Fischer T, Lahti A, Wilhelm K-P, Takiwaki H, Serup J: Guidelines for measurement skin colour and erythema. A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Dermatitis 1996;35:1-10.
52.
Bouchemal K, Briançon S, Perrier E, Fessi H: Nano-emulsion formulation using spontaneous emulsification: solvent, oil and surfactant optimisation. Int J Pharm 2004;280:241-251.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.