Intravitreal injection of TA-III with sustained release to simultaneously impart anti-inflammatory, antioxidative, and vascular remodeling activities in diabetic retinopathy

Diabetes negatively impacts vision and retinal function. However, current therapeutic options for diabetic retinopathy (DR) often present limitations, including targeting specific pathways, short duration of action, and need for frequent injections. Timosaponin AIII (TA-III) exhibited the potential...

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Main Authors: Jie Zhang, Yu Liu, Yu Gong, Yanyu Shangguan, Pengli Wang, Yanlong Bi, Yong Xu, Bo Tao, Bing Li
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Materials & Design
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Online Access:http://www.sciencedirect.com/science/article/pii/S0264127525002527
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author Jie Zhang
Yu Liu
Yu Gong
Yanyu Shangguan
Pengli Wang
Yanlong Bi
Yong Xu
Bo Tao
Bing Li
author_facet Jie Zhang
Yu Liu
Yu Gong
Yanyu Shangguan
Pengli Wang
Yanlong Bi
Yong Xu
Bo Tao
Bing Li
author_sort Jie Zhang
collection DOAJ
description Diabetes negatively impacts vision and retinal function. However, current therapeutic options for diabetic retinopathy (DR) often present limitations, including targeting specific pathways, short duration of action, and need for frequent injections. Timosaponin AIII (TA-III) exhibited the potential of anti-inflammation, anti-oxidative stress and promoting vascular remodeling abilities from bioinformatics analysis tool. Additionally, polyethylene glycol succinimide succinate [PEG-(SS)2]-human serum albumin (HSA) (Hp) hydrogel, known for its excellent biocompatibility and sustained drug release properties, was employed to encapsulate TA-III to exhibit a long-acting, sustained release profile. In vitro results demonstrated that the TA-III/Hp hydrogel upregulated the expression of vascular endothelial growth factor receptor 2 and zonula occludens-1, while reducing the level of vascular endothelial growth factor A. We further observed a significant reduction in the levels of reactive oxygen species, malondialdehyde, interleukin-1β, interleukin-6, and tumor necrosis factor-α under high glucose conditions by using the TA-III/Hp hydrogel in retinal pigment epithelium cells. Notably, intravitreal delivery of TA-III/Hp hydrogel in the DR mouse model effectively increased retinal thickness and numbers of mature blood vessels, while inhibiting oxidative stress and inflammatory factor levels. In conclusion, intravitreal injection of TA-III/Hp hydrogel facilitates sustained release of TA-III, simultaneously providing anti-inflammatory, antioxidative, and vascular remodeling effects in DR.
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spelling doaj-art-aef9cbe56cb5471dbf53097199ffd8d72025-08-20T03:22:04ZengElsevierMaterials & Design0264-12752025-05-0125311383210.1016/j.matdes.2025.113832Intravitreal injection of TA-III with sustained release to simultaneously impart anti-inflammatory, antioxidative, and vascular remodeling activities in diabetic retinopathyJie Zhang0Yu Liu1Yu Gong2Yanyu Shangguan3Pengli Wang4Yanlong Bi5Yong Xu6Bo Tao7Bing Li8Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, ChinaDepartment of Ophthalmology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, ChinaDepartment of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, ChinaDepartment of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, ChinaDepartment of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, ChinaDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China; Department of Plastic and Burn Surgery, the Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, China; Corresponding authors.Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China; Corresponding authors.Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China; Corresponding authors.Diabetes negatively impacts vision and retinal function. However, current therapeutic options for diabetic retinopathy (DR) often present limitations, including targeting specific pathways, short duration of action, and need for frequent injections. Timosaponin AIII (TA-III) exhibited the potential of anti-inflammation, anti-oxidative stress and promoting vascular remodeling abilities from bioinformatics analysis tool. Additionally, polyethylene glycol succinimide succinate [PEG-(SS)2]-human serum albumin (HSA) (Hp) hydrogel, known for its excellent biocompatibility and sustained drug release properties, was employed to encapsulate TA-III to exhibit a long-acting, sustained release profile. In vitro results demonstrated that the TA-III/Hp hydrogel upregulated the expression of vascular endothelial growth factor receptor 2 and zonula occludens-1, while reducing the level of vascular endothelial growth factor A. We further observed a significant reduction in the levels of reactive oxygen species, malondialdehyde, interleukin-1β, interleukin-6, and tumor necrosis factor-α under high glucose conditions by using the TA-III/Hp hydrogel in retinal pigment epithelium cells. Notably, intravitreal delivery of TA-III/Hp hydrogel in the DR mouse model effectively increased retinal thickness and numbers of mature blood vessels, while inhibiting oxidative stress and inflammatory factor levels. In conclusion, intravitreal injection of TA-III/Hp hydrogel facilitates sustained release of TA-III, simultaneously providing anti-inflammatory, antioxidative, and vascular remodeling effects in DR.http://www.sciencedirect.com/science/article/pii/S0264127525002527Diabetic retinopathyTimosaponin AIIIHydrogelAnti-inflammationAnti-oxidative stressVascular remodeling
spellingShingle Jie Zhang
Yu Liu
Yu Gong
Yanyu Shangguan
Pengli Wang
Yanlong Bi
Yong Xu
Bo Tao
Bing Li
Intravitreal injection of TA-III with sustained release to simultaneously impart anti-inflammatory, antioxidative, and vascular remodeling activities in diabetic retinopathy
Materials & Design
Diabetic retinopathy
Timosaponin AIII
Hydrogel
Anti-inflammation
Anti-oxidative stress
Vascular remodeling
title Intravitreal injection of TA-III with sustained release to simultaneously impart anti-inflammatory, antioxidative, and vascular remodeling activities in diabetic retinopathy
title_full Intravitreal injection of TA-III with sustained release to simultaneously impart anti-inflammatory, antioxidative, and vascular remodeling activities in diabetic retinopathy
title_fullStr Intravitreal injection of TA-III with sustained release to simultaneously impart anti-inflammatory, antioxidative, and vascular remodeling activities in diabetic retinopathy
title_full_unstemmed Intravitreal injection of TA-III with sustained release to simultaneously impart anti-inflammatory, antioxidative, and vascular remodeling activities in diabetic retinopathy
title_short Intravitreal injection of TA-III with sustained release to simultaneously impart anti-inflammatory, antioxidative, and vascular remodeling activities in diabetic retinopathy
title_sort intravitreal injection of ta iii with sustained release to simultaneously impart anti inflammatory antioxidative and vascular remodeling activities in diabetic retinopathy
topic Diabetic retinopathy
Timosaponin AIII
Hydrogel
Anti-inflammation
Anti-oxidative stress
Vascular remodeling
url http://www.sciencedirect.com/science/article/pii/S0264127525002527
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