A biomimetic peptide-drug supramolecular hydrogel as eyedrops enables controlled release of ophthalmic drugs

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 gener-ated 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 con-centration. 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 elastic-ity 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 to-ward human corneal epithelial cells. Moreover, the in vivo experiment showed that the supramolecular hydrogels remarkably increased pre-corneal retention without ocular irritation, thereby showing appre-ciable 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.& COPY; 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

In this study, an antibiotic hydrogel eye drop was developed to extend the pre-corneal retention of drugs. The self-assembly ability of peptide-drug conjugate and the addition of calcium ions were utilized to improve drug delivery efficacy. This biomimetic design of antibiotic eye drops addresses the current issues of ocular drug delivery and provides potential solutions for treating bacterial keratitis.