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. 2019 Jan 24;9:522. doi: 10.1038/s41598-018-36682-9

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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AA permeation and retention results in pig ear skin. AA (A) 6 and (B) 24 h retention in the epidermis and dermis after application of AA-liposome formulations (DRV) and AA solution (AA). (C) Cumulative amount of AA permeated through the skin per cm² during 24 h. (D) AA calculated permeation flux. *p < 0.05 free AA vs DRV1, DRV2, DRV3 and DRV4 in the epidermis at 24 h. ^#p < 0.001 AA vs DRV5 in the epidermis at 24 h. **p < 0.001 DRV5 vs AA, DRV1, DRV2, DRV3 and DRV4 in the dermis at 6 and 24 h. ^†p > 0.05 DRV5 vs DRV1, DRV2, DRV3, DRV4 and AA. ***p > 0.05 DRV4 vs DRV2 and AA. ^###p > 0.05 DRV3 vs DRV2 and AA. ^##p > 0.05 flux DRV 1 vs DRV2 and DRV3 vs DRV4. Intrinsic AA present in pig skin is not represented in the graph for being under the method’s LOQ. Values are represented as mean ± SD.