Citation: Sim, J.; Gong, S.; Kang, G.; Jang, M.; Yang, H.; Park, J.; Kim, Y.; Lee, H.; Jung, H.; Kim, Y.; et al. Enhanced Micro-Channeling System via Dissolving Microneedle to Improve Transdermal Serum Delivery for Various Clinical Skincare Treatments. Pharmaceutics 2022, 14, 2804. https://doi.org/10.3390/ pharmaceutics14122804 Academic Editors: Guilan Quan and Kevin Ita Received: 5 October 2022 Accepted: 12 December 2022 Published: 14 December 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). pharmaceutics Article Enhanced Micro-Channeling System via Dissolving Microneedle to Improve Transdermal Serum Delivery for Various Clinical Skincare Treatments Jeeho Sim 1 , SeongDae Gong 1,2 , Geonwoo Kang 1,2 , Mingyu Jang 2 , Huisuk Yang 2 , Jaesung Park 3 , Youngchan Kim 3 , Hyunkyu Lee 1,2 , Hyunji Jung 1,2 , Youseong Kim 1 , Chansol Jeon 1,2 , Hyeri Ahn 1 , Minkyung Kim 1 , Jaibyung Choi 1 , Ho Lee 4,5,6 and Hyungil Jung 1,2, * 1 Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea 2 JUVIC Inc., No. 208, Digital-ro 272, Guro-gu, Seoul 08389, Republic of Korea 3 Graduate School, Department of Mechanical Engineering, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea 4 School of Convergence, Department of Robot and Smart System Engineering, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea 5 Institute of Nanophotonics Application, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 41566, Republic of Korea 6 Laser Application Center, Kyungpook National University, 70 Dongnae-ro, Dong-gu, Daegu 41061, Republic of Korea * Correspondence: hijung@yonsei.ac.kr Abstract: Topical liquid formulations, dissolving microneedles (DMNs), and microscale needles composed of biodegradable materials have been widely used for the transdermal delivery of active compounds for skincare. However, transdermal active compound delivery by topical liquid formula- tion application is inhibited by skin barriers, and the skincare efficacy of DMNs is restricted by the low encapsulation capacity and incomplete insertion. In this study, topical serum application via a dissolv- able micro-channeling system (DMCS) was used to enhance serum delivery through micro-channels embedded with DMNs. Transdermal serum delivery was evaluated after the topical-serum-only application and combinatorial serum application by assessing the intensity of allophycocyanin (APC) loaded with the serum in the porcine skin. APC intensity was significantly higher in the skin layer at a depth of 120–270 μm upon combinatorial serum application as compared to topical-serum-only application. In addition, the combinatorial serum application showed significantly improved efficacy in the clinical assessment of skin hydration, depigmentation, improvement of wrinkles, elasticity, dermal density, skin pores, and skin soothing without any safety issues compared to the serum-only application. The results indicate that combinatorial serum application with DMCS is a promising candidate for improving skincare treatments with optimal transdermal delivery of active compounds. Keywords: serum; topical application; dissolvable micro-channeling system; transdermal delivery; skin hydration; skin depigmentation; wrinkle improvement 1. Introduction Transdermal delivery of therapeutics or functional substrates, which are widely used for skin-mediated drug treatment, is patient friendly and can be used as an alternative for oral drug delivery, which causes drug degradation in the digestive system and has a low absorption rate [1–4]. Topical application of formulations, such as ointments and creams, is mostly used for various cosmetic skincare treatments, such as skin hydration, skin depigmentation, and anti-wrinkling [5–7]. They are also used for skin-mediated treatment targeting local skin diseases, such as skin melasma, atopic dermatitis, and psoriasis [8–11]. However, active compounds with high molecular weights have difficulty penetrating the stratum corneum, which acts as a barrier, thereby limiting drug performance to a low Pharmaceutics 2022, 14, 2804. https://doi.org/10.3390/pharmaceutics14122804 https://www.mdpi.com/journal/pharmaceutics