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• W4382518044 abstract "The rapid clearance of instilled drugs from the ocular surface due to tear flushing and excretion results in low drug bioavailability, necessitating the development of new drug delivery routes. Here, we generated an antibiotic hydrogel eye drop that can extend the pre-corneal retention of a drug after topical instillation to address the risk of side effects (e.g., irritation and inhibition of enzymes), resulting from frequent and high-dosage administrations of antibiotics used to obtain the desired therapeutic drug concentration. The covalent conjugation of small peptides to antibiotics (e.g., chloramphenicol) first endows the self-assembly ability of peptide-drug conjugate to generate supramolecular hydrogels. Moreover, the further addition of calcium ions, which are also widely present in endogenous tears, tunes the elasticity of supramolecular hydrogels, making them ideal for ocular drug delivery. The in vitro assay revealed that the supramolecular hydrogels exhibited potent inhibitory activities against both gram-negative (e.g., Escherichia coli) and gram-positive (e.g., Staphylococcus aureus) bacteria, whereas they were innocuous toward human corneal epithelial cells. Moreover, the in vivo experiment showed that the supramolecular hydrogels remarkably increased pre-corneal retention without ocular irritation, thereby showing appreciable therapeutic efficacy for treating bacterial keratitis. This work, as a biomimetic design of antibiotic eye drops in the ocular microenvironment, addresses the current issues of ocular drug delivery in the clinic and further provides approaches to improve the bioavailability of drugs, which may eventually open new directions to resolve the difficulty of ocular drug delivery. STATEMENT OF SIGNIFICANCE: Herein, we present a biomimetic design for antibiotic hydrogel eye drops mediated by calcium ions (Ca2+) in the ocular microenvironment, which can extend the pre-corneal retention of antibiotics after topical instillation. The mediation of Ca2+ which is widely present in endogenous tears, tunes the elasticity of hydrogels, making them ideal for ocular drug delivery. Since increasing the ocular retention of antibiotic eye drops enhances its action and reduces its adverse effects, this work may lead to an approach of peptide-drug-based supramolecular hydrogel for ocular drug delivery in clinics to combat ocular bacterial infections." @default.
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• W4382518044 date "2023-09-01" @default.
• W4382518044 modified "2023-09-30" @default.
• W4382518044 title "A biomimetic peptide–drug supramolecular hydrogel as eyedrops enables controlled release of ophthalmic drugs" @default.
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• W4382518044 doi "https://doi.org/10.1016/j.actbio.2023.06.036" @default.
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