Background: Horse oil (HO) has skin barrier restoration and skin-moisturizing effects. Although cream formulations have been used widely and safely, their limited penetration through the stratum corneum is a major obstacle to maximizing the cosmetic efficacy of HO. Therefore, we aimed to encapsulate HO in a cosmetic dissolving microneedle (DMN) for efficient transdermal delivery. Methods: To overcome these limitations of skin permeation, HO-loaded DMN (HO-DMN) patches were developed and evaluated for their efficacy and safety using in vitro and clinical studies. Results: Despite the lipophilic nature of HO, the HO-DMN patches had a sharp shape and uniform array, with an average length and tip diameter of 388.36 ± 16.73 and 38.54 ± 5.29 µm, respectively. The mechanical strength of the HO-DMN patches was sufficient (fracture force of 0.29 ± 0.01 N), and they could successfully penetrate pig skin. During the 4-week clinical evaluation, HO-DMN patches caused significant improvements in skin and dermal density, skin elasticity, and moisturization. Additionally, a brief safety assessment showed that the HO-DMN patches induced negligible adverse events. Conclusion: The HO-DMNs are efficient, safe, and convenient for wide use in cosmetic applications for skin barrier restoration and moisturization.

1.
Downing DT, Vi SWC: Skin surface lipids of the horse. Lipids 1980; 15: 323–327.
2.
Brooker E, Shorland F: Studies on the composition of horse oil. 1. Composition of horse oil in relation to the depot fats of other pasture-fed animals. Biochem J 1950; 46: 80.
3.
Shorland F, Bruce L, Jessop A: Studies on the composition of horse oil. 2. The component fatty acids of lipids from fatty tissues, muscle and liver. Biochem J 1952; 52: 400.
4.
Kucharekova M, Schalkwijk J, Van De Kerkhof P, Van De Valk P: Effect of a lipid-rich emollient containing ceramide 3 in experimentally induced skin barrier dysfunction. Contact Dermatitis 2002; 46: 331–338.
5.
Jungersted JM, Hellgren LI, Jemec GB, Agner T: Lipids and skin barrier function – a clinical perspective. Contact Dermatitis 2008; 58: 255–262.
6.
Darmstadt G, Mao-Qiang M, Chi E, Saha S, Ziboh V, Black R, Santosham M, Elias P: Impact of topical oils on the skin barrier: possible implications for neonatal health in developing countries. Acta Paediatr 2002; 91: 546–554.
7.
Daehnhardt D, Daehnhardt-Pfeiffer S, Schulte-Walter J, Neubourg T, Hanisch E, Schmetz C, Breuer M, Fölster-Holst R: The influence of two different foam creams on skin barrier repair of foot xerosis: a prospective, double-blind, randomised, placebo-controlled intra-individual study. Skin Pharmacol Physiol 2016; 29: 266–272.
8.
Mattson F, Lutton E: The specific distribution of fatty acids in the glycerides of animal and vegetable fats. J Biol Chem 1958; 233: 868–871.
9.
Kompaore F, Marty J, Dupont C: In vivo evaluation of the stratum corneum barrier function in blacks, Caucasians and Asians with two noninvasive methods. Skin Pharmacol Physiol 1993; 6: 200–207.
10.
Kim S, Dangol M, Kang G, Lahiji SF, Yang H, Jang M, Ma Y, Li C, Lee SG, Kim CH, Choi YW, Kim SJ, Ryu JH, Baek JH, Koh J, Jung H: Enhanced transdermal delivery by combined application of dissolving microneedle patch on serum-treated skin. Mol Pharm 2017; 14: 2024–2031.
11.
Puizina-Ivić N, Mirić L, Čarija A, Karlica D, Marasović D: Modern approach to topical treatment of aging skin. Colleg Antropol 2010; 34: 1145–1153.
12.
Grimes PE: The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups. Dermatol Surg 1999; 25: 18–22.
13.
Alster TS, Lupton JR: Prevention and treatment of side effects and complications of cutaneous laser resurfacing. Plast Reconstr Surg 2002; 109: 308–316.
14.
Bernstein LJ, Kauvar AN, Grossman MC, Geronemus RG: The short- and long-term side effects of carbon dioxide laser resurfacing. Dermatol Surg 1997; 23: 519–525.
15.
Lowe NJ, Maxwell CA, Patnaik R: Adverse reactions to dermal fillers. Dermatol Surg 2005; 31: 1626–1633.
16.
Naumann M, Jankovic J: Safety of botulinum toxin type A: a systematic review and meta-analysis. Curr Med Res Opin 2004; 20: 981–990.
17.
Oh J-H, Park H-H, Do K-Y, Han M, Hyun D-H, Kim C-G, Kim C-H, Lee SS, Hwang S-J, Shin S-C, Cho C-W: Influence of the delivery systems using a microneedle array on the permeation of a hydrophilic molecule, calcein. Eur J Pharm Biopharm 2008; 69: 1040–1045.
18.
Lee K, Lee CY, Jung H: Dissolving microneedles for transdermal drug administration prepared by stepwise controlled drawing of maltose. Biomaterials 2011; 32: 3134–3140.
19.
Park J-H, Allen MG, Prausnitz MR: Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J Control Release 2005; 104: 51–66.
20.
Kim M, Yang H, Kim H, Jung H: Novel cosmetic patches for wrinkle improvement: retinyl retinoate- and ascorbic acid-loaded dissolving microneedles. Int J Cosmet Sci 2014; 36: 207–212.
21.
Lee C, Yang H, Kim S, Kim M, Kang H, Kim N, An S, Koh J, Jung H: Evaluation of the anti-wrinkle effect of an ascorbic acid-loaded dissolving microneedle patch via a double-blind, placebo-controlled clinical study. Int J Cosmet Sci 2016; 38: 375–381.
22.
Kim S, Yang H, Kim M, Baek JH, Kim SJ, An SM, Koh JS, Seo R, Jung H: 4-n-butylresorcinol dissolving microneedle patch for skin depigmentation: a randomized, double-blind, placebo-controlled trial. J Cosmet Dermatol 2016; 15: 16–23.
23.
Choi JW, Kwon SH, Huh CH, Park KC, Youn SW: The influences of skin visco-elasticity, hydration level and aging on the formation of wrinkles: a comprehensive and objective approach. Skin Res Technol 2013; 19:e349–e355.
24.
Hiraishi Y, Nandakumar S, Choi S-O, Lee JW, Kim Y-C, Posey JE, Sable SB, Prausnitz MR: Bacillus Calmette-Guerin vaccination using a microneedle patch. Vaccine 2011; 29: 2626–2636.
25.
Chu LY, Ye L, Dong K, Compans RW, Yang C, Prausnitz MR: Enhanced stability of inactivated influenza vaccine encapsulated in dissolving microneedle patches. Pharm Res 2016; 33: 868–878.
26.
Park J, Seo J, Shin JU, Jeong DH, Kim JD, Lee KH: Efficacy of biodegradable microneedle patches on periorbital wrinkles. Korean J Dermatol 2014; 52: 597–607.
27.
Yang H, Kim S, Kang G, Lahiji SF, Jang M, Kim YM, Kim JM, Cho SN, Jung H: Centrifugal lithography: self-shaping of polymer microstructures encapsulating biopharmaceutics by centrifuging polymer drops. Adv Healthc Mater 2017, Epub ahead of print.
28.
Brown MB, Jones SA: Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin. J Eur Acad Dermatol Venereol 2005; 19: 308–318.
29.
Berardesca E: EEMCO guidance for the assessment of stratum corneum hydration: electrical methods. Skin Res Technol 1997; 3: 126–132.
30.
Rogiers V: EEMCO guidance for the assessment of transepidermal water loss in cosmetic sciences. Skin Pharmacol Physiol 2001; 14: 117–128.
31.
Kim S, Lee J, Lahiji SF, Kim S, Huh I, Ma Y, Yang H, Kang G, Jung H: Physicochemical study of ascorbic acid 2-glucoside loaded hyaluronic acid dissolving microneedles irradiated by electron beam and gamma ray. Carbohydrate Polymers 2018; 180: 297–303.
32.
Rittié L, Fisher GJ: Isolation and culture of skin fibroblasts. Methods Mol Med 2005; 117: 83–98.
33.
Hahn HJ, Jung HJ, Schrammek-Drusios MC, Lee SN, Kim JH, Kwon SB, An IS, An S, Ahn KJ: Instrumental evaluation of anti-aging effects of cosmetic formulations containing palmitoyl peptides, Silybum marianum seed oil, vitamin E and other functional ingredients on aged human skin. Exp Ther Med 2016; 12: 1171–1176.
34.
Aldag C, Teixeira DN, Leventhal PS: Skin rejuvenation using cosmetic products containing growth factors, cytokines, and matrikines: a review of the literature. Clin Cosmet Invest Dermatol 2016; 9: 411.
35.
Cua A, Wilhelm K-P, Maibach H: Elastic properties of human skin: relation to age, sex, and anatomical region. Arch Dermatol Res 1990; 282: 283–288.
36.
Mizukoshi K, Nakamura T, Oba A: The relationship between dermal papillary structure and skin surface properties, color, and elasticity. Skin Res Technol 2016; 22: 295–304.
37.
Tsukahara K, Tamatsu Y, Sugawara Y, Shimada K: Relationship between the depth of facial wrinkles and the density of the retinacula cutis. Arch Dermatol 2012; 148: 39–46.
38.
Moldovan M, Lahmar A, Bogdan C, Părăuan S, Tomuţă I, Crişan M: Formulation and evaluation of a water-in-oil cream containing herbal active ingredients and ferulic acid. Clujul Med 2017; 90: 212.
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.