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Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis.

作者信息

Cai Maoyu, Zhong Haiping, Wang Xindi, Li Liangpin, Zhou Xueyan, Wang Yan, Hua Xia, Guo Shutao, Yuan Xiaoyong

机构信息

Clinical 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, China.

出版信息

Bioact Mater. 2025 Apr 22;50:396-413. doi: 10.1016/j.bioactmat.2025.04.011. eCollection 2025 Aug.


DOI:10.1016/j.bioactmat.2025.04.011
PMID:40331212
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12051119/
Abstract

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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/423f23a1dace/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/5f7583255517/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/1de14ff0ed71/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/7f732aaebee8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/c5f563cc6eb1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/74708b494479/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/bc3d192fa5e0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/8f776384f6ec/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/3df80d6b4cbd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/416809c2fb2c/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/423f23a1dace/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/5f7583255517/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/1de14ff0ed71/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/7f732aaebee8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/c5f563cc6eb1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/74708b494479/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/bc3d192fa5e0/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/8f776384f6ec/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/3df80d6b4cbd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/416809c2fb2c/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a15/12051119/423f23a1dace/gr8.jpg

相似文献

[1]
Pathology-inspired collagen-binding thermosensitive micelle drops enable prolonged and efficient treatment of fungal keratitis.

Bioact Mater. 2025-4-22

[2]
Mucoadhesive Hybrid System of Silk Fibroin Nanoparticles and Thermosensitive In Situ Hydrogel for Amphotericin B Delivery: A Potential Option for Fungal Keratitis Treatment.

Polymers (Basel). 2024-1-3

[3]
Solid Dispersion Incorporated into Dissolving Microneedles for Improved Antifungal Activity of Amphotericin B: Study in a Fungal Keratitis Model.

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[4]
Multifunctional natamycin modified chondroitin sulfate eye drops with anti-inflammatory, antifungal and tissue repair functions possess therapeutic effects on fungal keratitis in mice.

Int J Biol Macromol. 2024-11

[5]
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Int J Pharm. 2019-10-31

[6]
Amphotericin B Ocular Films for Fungal Keratitis and a Novel 3D-Printed Microfluidic Ocular Lens Infection Model.

J Fungi (Basel). 2024-11-2

[7]
The preparation and therapeutic effects of β-glucan-specific nanobodies and nanobody-natamycin conjugates in fungal keratitis.

Acta Biomater. 2023-10-1

[8]
Ocular amphotericin B delivery by chitosan-modified nanostructured lipid carriers for fungal keratitis-targeted therapy.

J Liposome Res. 2016-9-7

[9]
MSCs helped reduce scarring in the cornea after fungal infection when combined with anti-fungal treatment.

BMC Ophthalmol. 2019-11-14

[10]
Alleviation of dry eye syndrome with one dose of antioxidant, anti-inflammatory, and mucoadhesive lysine-carbonized nanogels.

Acta Biomater. 2022-3-15

本文引用的文献

[1]
Alginate-functionalized nanoceria as ion-responsive eye drop formulation to treat corneal abrasion.

Carbohydr Polym. 2025-3-15

[2]
Biologically inspired bioactive hydrogels for scarless corneal repair.

Sci Adv. 2024-12-20

[3]
Comparison of eye drop retention time using fluorophotometry in three commercially available lubricant eye drops.

Optom Vis Sci. 2024-9-1

[4]
Magnetically attracting hydrogel reshapes iron metabolism for tissue repair.

Sci Adv. 2024-8-16

[5]
Oriented cellulose hydrogel: Directed tissue regeneration for reducing corneal leukoplakia and managing fungal corneal ulcers.

Bioact Mater. 2024-7-9

[6]
Hydrophobic binary mixtures containing amphotericin B as lipophilic solutions for the treatment of cutaneous leishmaniasis.

Int J Pharm. 2024-9-5

[7]
Rosmarinic acid-grafted gelatin nanogels for efficient diquafosol delivery in dry eye disease therapy.

J Control Release. 2024-9

[8]
Etiopathology, Epidemiology, Diagnosis, and Treatment of Fungal Keratitis.

ACS Infect Dis. 2024-7-12

[9]
Hypotonic, gel-forming delivery system for vaginal drug administration.

J Control Release. 2024-7

[10]
In situ gelling systems for ocular drug delivery.

J Control Release. 2024-7

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