Hyaluronic acid/silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasis
Systemic administration of methotrexate (MTX), widely regarded as one of the most effective treatments for psoriasis, poses significant challenges due to its high toxicity, limited solubility, and potential for adverse effects. Consequently, developing a topical form of MTX may offer a safer and mor...
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Elsevier
2025-06-01
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| Series: | International Journal of Pharmaceutics: X |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590156724000847 |
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| author | Lan Cheng Yanhua Zhang Qian Xu Zheng Li Zulan Liu Fangyin Dai |
| author_facet | Lan Cheng Yanhua Zhang Qian Xu Zheng Li Zulan Liu Fangyin Dai |
| author_sort | Lan Cheng |
| collection | DOAJ |
| description | Systemic administration of methotrexate (MTX), widely regarded as one of the most effective treatments for psoriasis, poses significant challenges due to its high toxicity, limited solubility, and potential for adverse effects. Consequently, developing a topical form of MTX may offer a safer and more effective strategy for psoriasis management. Silk fibroin (SF), a protein-based biomacromolecule, has shown considerable promise as a nanocarrier for sustained and targeted drug delivery, owing to its exceptional physicochemical and biological properties. This study aimed to develop and characterize a novel drug delivery nanocarrier for MTX using SF nanoparticles modified with hyaluronic acid (HA) and to assess their potential for skin-targeted drug delivery with reduced transdermal permeation. The nanoparticles were thoroughly characterized, demonstrating a uniform particle size, high drug-loading capacity, pH sensitivity, and excellent slow-release properties. In vitro and in vivo experiments further indicated that these nanoparticles effectively reduced psoriasis-induced inflammatory responses, including erythema and scaling, by inhibiting keratinocyte proliferation and decreasing levels of pro-inflammatory cytokines. The inclusion of HA improved nanoparticle targeting, particularly through interactions with overexpressed CD44 proteins in psoriatic skin, resulting in enhanced methotrexate accumulation at the sites of inflammation and improved therapeutic efficacy. Our findings suggest that HA/SF nanoparticles loaded with MTX represent a promising, safe transdermal delivery system for the localized treatment of psoriasis. |
| format | Article |
| id | doaj-art-b6ff0d41dbc242f7a059d938596ea2a9 |
| institution | OA Journals |
| issn | 2590-1567 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Pharmaceutics: X |
| spelling | doaj-art-b6ff0d41dbc242f7a059d938596ea2a92025-08-20T02:37:06ZengElsevierInternational Journal of Pharmaceutics: X2590-15672025-06-01910031210.1016/j.ijpx.2024.100312Hyaluronic acid/silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasisLan Cheng0Yanhua Zhang1Qian Xu2Zheng Li3Zulan Liu4Fangyin Dai5State Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China; Luoyang Central Hospital, No. 288 Zhongzhou middle road, Xigong district, Luoyang, Henan province, 471000, ChinaState Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China; Luoyang Central Hospital, No. 288 Zhongzhou middle road, Xigong district, Luoyang, Henan province, 471000, ChinaState Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China; Luoyang Central Hospital, No. 288 Zhongzhou middle road, Xigong district, Luoyang, Henan province, 471000, ChinaState Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China; Luoyang Central Hospital, No. 288 Zhongzhou middle road, Xigong district, Luoyang, Henan province, 471000, ChinaCorresponding authors.; State Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China; Luoyang Central Hospital, No. 288 Zhongzhou middle road, Xigong district, Luoyang, Henan province, 471000, ChinaCorresponding authors.; State Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China; Luoyang Central Hospital, No. 288 Zhongzhou middle road, Xigong district, Luoyang, Henan province, 471000, ChinaSystemic administration of methotrexate (MTX), widely regarded as one of the most effective treatments for psoriasis, poses significant challenges due to its high toxicity, limited solubility, and potential for adverse effects. Consequently, developing a topical form of MTX may offer a safer and more effective strategy for psoriasis management. Silk fibroin (SF), a protein-based biomacromolecule, has shown considerable promise as a nanocarrier for sustained and targeted drug delivery, owing to its exceptional physicochemical and biological properties. This study aimed to develop and characterize a novel drug delivery nanocarrier for MTX using SF nanoparticles modified with hyaluronic acid (HA) and to assess their potential for skin-targeted drug delivery with reduced transdermal permeation. The nanoparticles were thoroughly characterized, demonstrating a uniform particle size, high drug-loading capacity, pH sensitivity, and excellent slow-release properties. In vitro and in vivo experiments further indicated that these nanoparticles effectively reduced psoriasis-induced inflammatory responses, including erythema and scaling, by inhibiting keratinocyte proliferation and decreasing levels of pro-inflammatory cytokines. The inclusion of HA improved nanoparticle targeting, particularly through interactions with overexpressed CD44 proteins in psoriatic skin, resulting in enhanced methotrexate accumulation at the sites of inflammation and improved therapeutic efficacy. Our findings suggest that HA/SF nanoparticles loaded with MTX represent a promising, safe transdermal delivery system for the localized treatment of psoriasis.http://www.sciencedirect.com/science/article/pii/S2590156724000847PsoriasisMethotrexateSilk fibroin nanoparticlesHyaluronic acidInflammatory factor |
| spellingShingle | Lan Cheng Yanhua Zhang Qian Xu Zheng Li Zulan Liu Fangyin Dai Hyaluronic acid/silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasis International Journal of Pharmaceutics: X Psoriasis Methotrexate Silk fibroin nanoparticles Hyaluronic acid Inflammatory factor |
| title | Hyaluronic acid/silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasis |
| title_full | Hyaluronic acid/silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasis |
| title_fullStr | Hyaluronic acid/silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasis |
| title_full_unstemmed | Hyaluronic acid/silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasis |
| title_short | Hyaluronic acid/silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasis |
| title_sort | hyaluronic acid silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasis |
| topic | Psoriasis Methotrexate Silk fibroin nanoparticles Hyaluronic acid Inflammatory factor |
| url | http://www.sciencedirect.com/science/article/pii/S2590156724000847 |
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