Dexamethasone-loaded ROS stimuli-responsive nanogels for topical ocular therapy of corneal neovascularization.
J Control Release
; 372: 874-884, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38977133
ABSTRACT
Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin ß1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dexamethasone
/
Corneal Neovascularization
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Reactive Oxygen Species
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
J Control Release
Journal subject:
FARMACOLOGIA
Year:
2024
Document type:
Article
Country of publication: