Self-Assembling Peptide Nanofiber Hydrogels for Controlled Ocular Delivery of Timolol Maleate KaravasiliChristina KomnenouAnastasia L. KatsamenisOrestis CharalampidouGlykeria KofidouEvangelia AndreadisDimitrios KoutsopoulosSotirios FatourosDimitrios G. 2017 The self-assembling peptides Ac-(RADA)<sub>4</sub>-CONH<sub>2</sub> and Ac-(IEIK)<sub>3</sub>I-CONH<sub>2</sub>, which form hydrogels in physiological conditions, were evaluated as carriers for ocular delivery of the β-blocker timolol maleate. Electron microscopy studies revealed that hydrogels contain nanofibers, whereas rheological studies showed that the Ac-(IEIK)<sub>3</sub>I-CONH<sub>2</sub> self-assembles in a stiffer hydrogel compared with the Ac-(RADA)<sub>4</sub>-CONH<sub>2</sub> peptide. The in vitro release and ex vivo permeation studies demonstrated controlled release and transport of the drug through the cornea, which depended on the self-assembling peptide sequence. In vivo studies in rabbits showed significant increase in the area under the concentration–time curve (AUC) after administration of the drug through the Ac-(RADA)<sub>4</sub>-CONH<sub>2</sub> hydrogel compared to drug solution, whereas a sustained reduction of intraocular pressure for up to 24 h after instillation was achieved for both drug-loaded hydrogels. Histological studies revealed good ocular tolerability upon application of the formulations, suggesting that self-assembling peptide hydrogels are promising systems for sustained ocular drug delivery.