Biotechnology and Bioprocess Engineering 2023; 28(3): 473-482  
Locoregional Melanoma Therapy by Tissue Adhesive Microneedle Patch-assisted Trans-tumoral Delivery of Anticancer Drug
Junghwan Heo, Eun Young Jeon, Kye Il Joo, and Hyung Joon Cha
Junghwan Heo†, Eun Young Jeon+,†, Hyung Joon Cha*
Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 37673, Korea
Tel: +82-54-279-2280; Fax: +82-54-279-5528
E-mail: hjcha@postech.ac.kr
Kye Il Joo
Division of Chemical Engineering and Materials Science, Ewha Womans University, Seoul 03760, Korea
+Present address: Department of Dermatology, Columbia University Irving Medical Center, New York, NY 10032, USA
†Junghwan Heo and Eun Young Jeon contributed equally to this work.
Received: October 5, 2022; Revised: November 6, 2022; Accepted: November 22, 2022; Published online: June 30, 2023.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Melanoma is one of the most threatening cancers due to its metastatic capacity and its incidence is recently increasing due to ozone depletion and excessive exposure to ultraviolet. Adjuvant therapy after primary surgical resection is commonly used to prevent tumor recurrence. However, its clinical outcome is not often satisfactory, mainly due to insufficient local accumulation and the systemic toxicity of antitumor drugs. Herein, we reported a self-biodegradable tissue adhesive microneedle (MN) patch for localized and sustained delivery of doxorubicin (DOX) via microchannels for melanoma growth inhibition. DOX-loaded MN patches were fabricated by casting bioengineered mussel adhesive protein (MAP) solution containing DOX onto poly (dimethyl siloxane) molds with MN-shaped cavities under backside vacuum. The fabricated MAP-based MN patch enabled effective tissue insertion for fresh and living mice skins as well as firm surface adhesion. Notably, DOX-laden MN (DOXMN) patch significantly suppressed B16F10 melanoma cell proliferation in vitro, while drug-free MN patch did not show any cytotoxicity for both NIH3T3 fibroblasts and B16F10 melanoma cells. In a melanoma-bearing mice model, DOX-MN patch treatment induced greater antitumor efficacy as demonstrated by significant decrease in tumor volume and weight and larger necrotic region compared with intratumoral injection of free DOX. We expect that this strategy can also integrate with other immunomodulators to provide further combinative therapy for effectively eradicating tumors.
Keywords: mussel adhesive protein, tissue adhesive microneedle patch, transdermal delivery, doxorubicin, melanoma treatment

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