Sustained release of cathepsin D/cathepsin K from injectable hydrogel microspheres in anti-photoaging

There have been various interventions for photoaging skin, such as retinoic acid treatment and laser therapy. However, more precise, secure, and effective technologies and materials were still need to be explored. Cathepsin D (CTSD) repairs the epidermal barrier in chronic photodamaged skin through...

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Main Authors: Wenyi Hou, Zhaoyi Lin, Xinling Chen, Yu Sun, Yao Lin, Mengran Peng, Feng Zhou, Huamin Jiang, Yan Li, Yue Zheng
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425007203
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author Wenyi Hou
Zhaoyi Lin
Xinling Chen
Yu Sun
Yao Lin
Mengran Peng
Feng Zhou
Huamin Jiang
Yan Li
Yue Zheng
author_facet Wenyi Hou
Zhaoyi Lin
Xinling Chen
Yu Sun
Yao Lin
Mengran Peng
Feng Zhou
Huamin Jiang
Yan Li
Yue Zheng
author_sort Wenyi Hou
collection DOAJ
description There have been various interventions for photoaging skin, such as retinoic acid treatment and laser therapy. However, more precise, secure, and effective technologies and materials were still need to be explored. Cathepsin D (CTSD) repairs the epidermal barrier in chronic photodamaged skin through increasing TGase-1 expression and activity. Cathepsin K (CTSK) affects the metabolism of skin elastic fibers. Therefore, gelatin/alginate composite hydrogel microspheres loaded with CTSD or CTSK were fabricated. The microspheres with an average size of 79.8 ± 30.4 μm were stable in PBS (pH 7.4) for 5 days and then disintegrated in vitro. 0.1 mg/mL of microspheres continuously released 12–13 ng/mL CTSD or CTSK for the first three consecutive days. In vivo, the microspheres were almost completed degraded on day 7 after the subcutaneous injection. The biosafety and efficacy of CTSD- and CTSK- microspheres were confirmed in vitro and in vivo. They reduced ROS and inhibited the degradation of skin collagen and elastic fibers by upregulating Nrf2 and downregulating MMP-1 and MMP-3, which reversed photodamage of skin induced by UV. In conclusion, the gelatin/alginate composite microspheres loaded with CTSD or CTSK showed a great potential for chronic photodamaged skin.
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spelling doaj-art-0c5f4e46f44247cbbed53ddff9d80f952025-08-20T03:45:03ZengElsevierMaterials Today Bio2590-00642025-10-013410215010.1016/j.mtbio.2025.102150Sustained release of cathepsin D/cathepsin K from injectable hydrogel microspheres in anti-photoagingWenyi Hou0Zhaoyi Lin1Xinling Chen2Yu Sun3Yao Lin4Mengran Peng5Feng Zhou6Huamin Jiang7Yan Li8Yue Zheng9Department of Dermato-Venerology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR ChinaSchool of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR ChinaDepartment of Dermato-Venerology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR ChinaDermatology Department, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, PR China; Department of Dermato-Venerology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR ChinaDepartment of Dermato-Venerology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China; Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, PR ChinaDermatology Department, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, PR China; Department of Dermato-Venerology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR ChinaDepartment of Dermato-Venerology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR ChinaSchool of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR ChinaSchool of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China; Corresponding author. School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China.Dermatology Department, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, PR China; Department of Dermato-Venerology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, PR China; Corresponding author. Department of Dermato-Venerology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510630, PR China.There have been various interventions for photoaging skin, such as retinoic acid treatment and laser therapy. However, more precise, secure, and effective technologies and materials were still need to be explored. Cathepsin D (CTSD) repairs the epidermal barrier in chronic photodamaged skin through increasing TGase-1 expression and activity. Cathepsin K (CTSK) affects the metabolism of skin elastic fibers. Therefore, gelatin/alginate composite hydrogel microspheres loaded with CTSD or CTSK were fabricated. The microspheres with an average size of 79.8 ± 30.4 μm were stable in PBS (pH 7.4) for 5 days and then disintegrated in vitro. 0.1 mg/mL of microspheres continuously released 12–13 ng/mL CTSD or CTSK for the first three consecutive days. In vivo, the microspheres were almost completed degraded on day 7 after the subcutaneous injection. The biosafety and efficacy of CTSD- and CTSK- microspheres were confirmed in vitro and in vivo. They reduced ROS and inhibited the degradation of skin collagen and elastic fibers by upregulating Nrf2 and downregulating MMP-1 and MMP-3, which reversed photodamage of skin induced by UV. In conclusion, the gelatin/alginate composite microspheres loaded with CTSD or CTSK showed a great potential for chronic photodamaged skin.http://www.sciencedirect.com/science/article/pii/S2590006425007203Degradable microspheresPhotoagingCathepsin DCathepsin KSkin
spellingShingle Wenyi Hou
Zhaoyi Lin
Xinling Chen
Yu Sun
Yao Lin
Mengran Peng
Feng Zhou
Huamin Jiang
Yan Li
Yue Zheng
Sustained release of cathepsin D/cathepsin K from injectable hydrogel microspheres in anti-photoaging
Materials Today Bio
Degradable microspheres
Photoaging
Cathepsin D
Cathepsin K
Skin
title Sustained release of cathepsin D/cathepsin K from injectable hydrogel microspheres in anti-photoaging
title_full Sustained release of cathepsin D/cathepsin K from injectable hydrogel microspheres in anti-photoaging
title_fullStr Sustained release of cathepsin D/cathepsin K from injectable hydrogel microspheres in anti-photoaging
title_full_unstemmed Sustained release of cathepsin D/cathepsin K from injectable hydrogel microspheres in anti-photoaging
title_short Sustained release of cathepsin D/cathepsin K from injectable hydrogel microspheres in anti-photoaging
title_sort sustained release of cathepsin d cathepsin k from injectable hydrogel microspheres in anti photoaging
topic Degradable microspheres
Photoaging
Cathepsin D
Cathepsin K
Skin
url http://www.sciencedirect.com/science/article/pii/S2590006425007203
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