Localized co-delivery of CNTF and FK506 using a thermosensitive hydrogel for retina ganglion cells protection after traumatic optic nerve injury
Open accessAbstract
Following the traumatic axonal injury in the optic nerve, the failure of retrograde axonal transport to continuously supply neurotrophins from the brain to retina results in deprivation of neurotrophins in retinal ganglion cells (RGCs), which in turn can modulate the fate of RGCs toward apoptosis and thereby impede axon regeneration. In this study, a ciliary neurotrophic factor (CNTF) loaded thermo-sensitive hydrogel was designed and developed as a localized drug depot to restore neurotrophins supply following axon injury. Besides, following traumatic axon injury, overactive immune responses cause neurotoxicity and induce scar formation which together constitutes the major hindrances for axon regeneration. Thus, the FK506, a hydrophobic macrolide immunosuppressant, was co-loaded into the hydrogel after encapsulating it into a polymeric micelle. The materials can undergo sol-to-gel transition within minutes under a physiological pH of 37 °C. The release of drugs from the hydrogel exhibited a sustainable profile in vitro. The optic nerve was exposed by surgical procedure and the animal model was prepared by crushing the nerve with a reverse clamp. For the localized delivery to the optic nerve, a pre-hydrogel liquid containing chitosan, FK506 (in micelle), CNTF, and the gelling agent was directly smeared on the injured site, which gelled under physiological condition. This co-delivery system exhibited in vivo RGCs protective effect against the adverse effects caused by traumatic optic nerve injury, indicating the potential of this drug delivery system for effective optic nerve repair and this strategy may provide promising platforms for localized drug delivery in various other therapies.
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It has also demonstrated potent efficacy in protecting retinal ganglion cells (RGCs) and repairing the optic nerve in a rabbit model of optic nerve injury.
“It has also demonstrated potent efficacy in protecting retinal ganglion cells (RGCs) and repairing the optic nerve in a rabbit model of optic nerve injury (Fig. 5b).”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [114]
The Results section (‘In vivo RGCs protective effects’; page unavailable) reports fewer RGC deaths and more regular retinal morphology after hydrogel treatment in rabbits, suggesting potential RGC protection. It does not demonstrate optic nerve repair, and ‘potent efficacy’ states the protective finding more strongly than the paper does. (LLM, conf=0.90)
Experimental — accuracy not yet measuredWang et al. developed an FK 506-coated PEG-PBG polymeric micelle (292 nm in size) co-encapsulated with ciliary neurotrophic factor (CNTF) in a temperature-sensitive hydrogel.
“For instance, Wang et al. developed an FK 506-coated PEG-PBG polymeric micelle (292 nm in size) that was co-encapsulated with ciliary neurotrophic factor (CNTF) in a temperature-sensitive hydrogel [114].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [114]
The Methods and materials and Introduction sections describe an FK506-loaded PEG–PBG micelle co-encapsulated with CNTF in a thermosensitive hydrogel. The Results section reports a DLS peak size of 303 nm, not 292 nm; the paper also describes FK506 as loaded into the micelle, rather than coating it. Page numbers were not supplied. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThis chitosan-based hydrogel could gel at 37 °C under physiological conditions, thereby reducing the release rate of FK 506 compared with micelles alone.
“This chitosan-based hydrogel could gel at 37 °C under physiological conditions, thereby reducing the release rate of FK 506 compared with micelles alone.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [114]
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- Authors
- Wang, D., Luo, M., Huang, B., Gao, W., Jiang, Y., Li, Q., Nan, K., & Lin, S.
- Affiliations
- Wenzhou Medical University (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Nan, Kaihui
- Lin, Sen
- Venue
- Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2020-01
- Volume
- 27
- Issue
- 1
- Pages
- 556-564
- ISSN
- 1071-7544 (ISSN-L)
- 1521-0464
- PMC
- PMC7241497
- OpenAlex
- W3021969174
- Cited by
- 38
- References
- 40
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 1
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Delivery (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Key Research and Development Plan (2016YFC1101201)
- the National Natural Science Foundation of China (31901735, 31600807)
- the Provincial Natural Science Foundation of Zhejiang, China (LY19H120002)
- Wenzhou Medical University (K171204)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- ciliary neurotrophic factor, FK506, thermosensitive hydrogel, retinal ganglion cells, traumatic optic nerve injury, axonal injury, local drug delivery, co-delivery, polymeric micelles, chitosan, neuroprotection, axon regeneration, immunosuppression, scar formation, sol-gel transition
- MeSH terms
- Animals, Axons, Cell Survival, Cells, Cultured, Disease Models, Animal, Drug Carriers, Hot Temperature, Micelles, Nerve Regeneration, Optic Nerve, Rabbits, Retinal Ganglion Cells, Rheology, Tacrolimus, Rats, Sprague-Dawley, Hydrogels, Optic Nerve Injuries, Ciliary Neurotrophic Factor, Rats, Nanoparticles, Drug Liberation
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