Injectable drug-loaded thermosensitive hydrogel delivery system for protecting retina ganglion cells in traumatic optic neuropathy

Lei Wang; Yan Jiang; Yili Yao; Yudan Deng; Zhiqiang Liu; Jiangtao Ding; Wenwen Wang; Hao Chen; Kaihui Nan; Lingli Li

doi:10.1093/rb/rbae124

Injectable drug-loaded thermosensitive hydrogel delivery system for protecting retina ganglion cells in traumatic optic neuropathy

Regen Biomater. 2024 Oct 24:11:rbae124. doi: 10.1093/rb/rbae124. eCollection 2024.

Authors

Lei Wang^{1

2

3

4}, Yan Jiang^{1

2

5}, Yili Yao¹, Yudan Deng¹, Zhiqiang Liu¹, Jiangtao Ding¹, Wenwen Wang⁶, Hao Chen^{1

2}, Kaihui Nan^{1

2}, Lingli Li^{1

2

3

7}

Affiliations

¹ School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
² State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
³ Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China.
⁴ The Affiliated Xiangshan Hospital, Wenzhou Medical University, Ningbo, Zhejiang 315700, China.
⁵ Refractive Surgery Center, Chongqing Eye and Vision Care Hospital, Chongqing 40042, China.
⁶ Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China.
⁷ Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China.

Abstract

Currently, generalized therapy for traumatic optic neuropathy (TON) is lacking. Various strategies have been developed to protect and regenerate retinal ganglion cells (RGCs) after TON. Intravitreal injection of supplements has been approved as a promising approach, although serious concerns, such as low delivery efficacy and pain due to frequent injections, remain. In this study, we tested an injectable thermosensitive hydrogel drug delivery system engineered to deliver ciliary neurotrophic factor (CNTF) and triamcinolone acetonide (TA). The results of rheological studies showed that the prepared drug-loaded hydrogel possessed a suitable mechanical modulus of ∼300 Pa, consistent with that of vitreum. The hydrogel exhibited thermosensitive with sustained drug release performance. In vitro co-culture of the CNTF-loaded hydrogel system with primary RGCs also induced significant axon regeneration, with 38.5% increase in neurite length, indicating the regenerative response of the thermosensitive hydrogel drug delivery system. A Sprague-Dawley rat optic nerve crush model was constructed and applied to determine the neuroprotective and regenerative capacities of the system. The results demonstrated that a single intravitreal injection of the drug-loaded hydrogel (PLGA-PEG-PLGA + TA or PLGA-PEG-PLGA + CNTF) significantly increased RGC survival at both 14 and 28 days. The RGC survival rate was 31.05 ± 1.41% for the drug-loaded hydrogel system (the control group was 16.79 ± 1.50%) at Day 28. These findings suggest that the injectable drug-loaded thermosensitive hydrogel delivery system is a promising therapeutic tool for treating optic nerve degeneration.

Keywords: CNTF; TA; TON; retinal ganglion cells; thermosensitive hydrogel.