Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis
Fungal keratitis (FK) is a challenging-to-manage blinding corneal infectious disease that often leads to severe sequelae, such as corneal leukoplakia regardless of curative care. Moreover, the unique anatomical structure and tear turnover of the eye significantly limit the bioavailability and therap...
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| Language: | English |
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KeAi Communications Co., Ltd.
2025-08-01
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| Series: | Bioactive Materials |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25001501 |
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| author | Maoyu Cai Haiping Zhong Xindi Wang Liangpin Li Xueyan Zhou Yan Wang Xia Hua Shutao Guo Xiaoyong Yuan |
| author_facet | Maoyu Cai Haiping Zhong Xindi Wang Liangpin Li Xueyan Zhou Yan Wang Xia Hua Shutao Guo Xiaoyong Yuan |
| author_sort | Maoyu Cai |
| collection | DOAJ |
| description | Fungal keratitis (FK) is a challenging-to-manage blinding corneal infectious disease that often leads to severe sequelae, such as corneal leukoplakia regardless of curative care. Moreover, the unique anatomical structure and tear turnover of the eye significantly limit the bioavailability and therapeutic efficacy of traditional eye drops. Inspired by the unique pathological features of corneal ulcers, we report a thermosensitive multifunctional eye drop, designated PX-TA, based on a poloxamer (PX) and a collagen-adhesive tannic acid (TA), for prolonged and efficient treatment of FK. PX-TA transforms into a gel at body temperature and adheres to exposed collagen at the ulcer site; this significantly improves the corneal retention time and bioavailability. PX-TA maintains corneal retention for at least 90 min, substantially exceeding both the 15-min limit of commercial mucoadhesive eye drops and the 30-min threshold of conventional in situ gels. When loaded with amphotericin B (AmB), once-daily PX-TA-AmB administration effectively suppresses inflammation and corneal scarring, demonstrating superior efficacy over six-times-daily free AmB drops and a good safety profile. Mechanistic investigations reveal that PX-TA-AmB mediates its therapeutic effects through the MAPK6/PI3K/AKT signaling pathway. Moreover, the metal-chelating properties of TA inhibit the copper-dependent enzyme lysyl oxidase (LOX), resulting in reduced matrix fibrosis. Overall, the use of PX-TA-AmB drops represents a simplified yet effective strategy for the potential clinical management of FK, inspiring the design of eye drop formulations. |
| format | Article |
| id | doaj-art-83e153d8af314e87b73d9eb606bcbedb |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-83e153d8af314e87b73d9eb606bcbedb2025-08-20T03:45:15ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-08-015039641310.1016/j.bioactmat.2025.04.011Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitisMaoyu Cai0Haiping Zhong1Xindi Wang2Liangpin Li3Xueyan Zhou4Yan Wang5Xia Hua6Shutao Guo7Xiaoyong Yuan8Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, 300020, China; Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, 300020, ChinaKey Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China; School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, 510260, ChinaClinical College of Ophthalmology, Tianjin Medical University, Tianjin, 300020, China; Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, 300020, ChinaTianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, 300020, ChinaSchool of Medicine, Nankai University, Tianjin, 300071, ChinaTianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, 300020, China; Corresponding author.Aier Eye Institute, Changsha, 410015, China; Aier Eye Hospital, Tianjin University, Tianjin, 300110, China; Corresponding author. Aier Eye Institute, Changsha, 410015, China.Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China; Corresponding author.Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin, 300020, China; Corresponding author.Fungal keratitis (FK) is a challenging-to-manage blinding corneal infectious disease that often leads to severe sequelae, such as corneal leukoplakia regardless of curative care. Moreover, the unique anatomical structure and tear turnover of the eye significantly limit the bioavailability and therapeutic efficacy of traditional eye drops. Inspired by the unique pathological features of corneal ulcers, we report a thermosensitive multifunctional eye drop, designated PX-TA, based on a poloxamer (PX) and a collagen-adhesive tannic acid (TA), for prolonged and efficient treatment of FK. PX-TA transforms into a gel at body temperature and adheres to exposed collagen at the ulcer site; this significantly improves the corneal retention time and bioavailability. PX-TA maintains corneal retention for at least 90 min, substantially exceeding both the 15-min limit of commercial mucoadhesive eye drops and the 30-min threshold of conventional in situ gels. When loaded with amphotericin B (AmB), once-daily PX-TA-AmB administration effectively suppresses inflammation and corneal scarring, demonstrating superior efficacy over six-times-daily free AmB drops and a good safety profile. Mechanistic investigations reveal that PX-TA-AmB mediates its therapeutic effects through the MAPK6/PI3K/AKT signaling pathway. Moreover, the metal-chelating properties of TA inhibit the copper-dependent enzyme lysyl oxidase (LOX), resulting in reduced matrix fibrosis. Overall, the use of PX-TA-AmB drops represents a simplified yet effective strategy for the potential clinical management of FK, inspiring the design of eye drop formulations.http://www.sciencedirect.com/science/article/pii/S2452199X25001501 |
| spellingShingle | Maoyu Cai Haiping Zhong Xindi Wang Liangpin Li Xueyan Zhou Yan Wang Xia Hua Shutao Guo Xiaoyong Yuan Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis Bioactive Materials |
| title | Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis |
| title_full | Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis |
| title_fullStr | Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis |
| title_full_unstemmed | Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis |
| title_short | Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis |
| title_sort | pathology inspired collagen binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25001501 |
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