Table Info

Table 1.

Summary of recent applications of hydrogels as ocular surface DDS

Disease	Hydrogel composition	Delivery route & active ingredients	Study phase	Release duration	Advantages & limitations	Reference
Dry eye disease (DED)	Aldehyde-functionalized F127	Multifunctional antioxidant Cu_2-xSe nanoparticles	In vitro; in vivo (mice)	Up to 72 hours	Thermosensitive; scavenging of reactive oxygen species; reduced cell damage & apoptosis in cornea and conjunctiva; have not been tested on human patients with DED	[60]
	Phenylboronic acid-grafted carboxymethyl cellulose	Glutathione (GSH)	In vitro; in vivo (rabbits)	50 hours	Reduce inflammation caused by preservative in eye drops (benzalkonium chloride); have not been tested on human patients with DED	[90]
	Carbomer	Cyclosporine A	Phase III clinical trial	-	Once-a-day treatment for moderate to severe DED; short follow-up duration; long-term safety remains unknown; safety profile compared to other DED topical medications remains unknown; patients with surgery-related DED, drug-related DED, or contact lens wear are excluded from the study	[61]
Glaucoma	Hydroxypropyl methylcellulose	Curcumin	In vitro; in vivo	7 days	Decrease inflammation & apoptosis; biocompatible; have only tested biocompatibility on normal animal models; have not tested on animals with glaucoma	[24]
	Chitosan	Pilocarpine	In vitro; in vivo (rabbits)	Within 4 hours	pH-Responsive; burst release that can suppress extreme IOP elevation; prevent damage of endothelium and retinal degeneration 4 hours post-application; the long-term safety profile remains unknown	[37]
	Mono-methacrylated β-cyclodextrin (β-CD) monomer; HEMA	Puerarin; curcumin	In vitro	Under redox conditions: 5 hours; under non-reducing conditions: 6 hours	Highly sensitive to reduced GSH; need to be tested on glaucomatous animal models	[36]
Corneal alkali burn	Hydroxypropyl methylcellulose & sodium hyaluronate	Imatinib	In vivo (mice)	6 hours	All ingredients used in the formulation are FAD-approved; simple process of formulation preparation; suitable for large-scale production; prompted corneal wound healing & alleviated inflammation; additional anti-scarring drug is needed to achieve greater treatment results	[41]
	Polyamino acid-based poly-S-nitrosothiols (PGlu-TEPA-SNAP)	Nitric oxide (NO)	In vitro; in vivo (mice)	More than 12 hours	Thermosensitive; effective therapeutic effects with minimal ocular complications compared to the traditional dexamethasone treatment; potential application in leptin-based or NO works for ocular therapy; potential application for reluctant corticosteroid therapy of injured cornea	[45]
	Oxidized chitosan; silk methacrylate (SilMA)	Black phosphorus quantum dots	In vitro; in vivo (mice)	-	Photocurable; pH-responsive; reduced corneal fibrosis & promoted ocular surface reshaping; neutralized free radicals under acidic conditions	[46]
	Oxidized chitosan; silk fibroin	DNase I	In vitro; in vivo (mouse)	7 days	Photocurable; expedited wound repair through increased migration of corneal stromal cells; the precise mechanism of the neutrophil extracellular trap neovascularization cascade effect remains unclear	[47]
Corneal neovascularization	Poloxamer-407 (pluronic F127); oxidized sodium alginate	Bone morphogenetic protein 4 (BMP4)	In vitro; in vivo (rats)	More than 72 hours	Thermosensitive; applied 3 times a day; reduce inflammation & alleviate corneal edema; reduced production costs; biocompatible	[54]
Corneal neovascularization	Self-assembling peptide	Aflibercept (Eylea); cell penetrating peptide	In vitro; in vivo (rabbits)	More than 25 hours	Neutralization of the negatively charged Eylea allowed the drug to penetrate the corneal stroma; prevent the formation of new abnormal vessels with minimal effect on normal vessels; potential application for treatment of diabetic retinopathy and AMD	[55]

DDS: drug delivery systems; IOP: intraocular pressure; HEMA: hydroxyethyl methacrylate; DNase I: deoxyribonuclease I; AMD: age-related macular degeneration; -: no data

Declarations

Author contributions

DT and KYW: Conceptualization, Writing—original draft, Writing—review & editing. LN: Visualization. SDT: Supervision.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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