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Self-Assembling Peptide Nanofiber Hydrogels for Controlled Ocular Delivery of Timolol Maleate
journal contribution
posted on 2017-11-04, 00:00 authored by Christina Karavasili, Anastasia Komnenou, Orestis L. Katsamenis, Glykeria Charalampidou, Evangelia Kofidou, Dimitrios Andreadis, Sotirios Koutsopoulos, Dimitrios G. FatourosThe
self-assembling peptides Ac-(RADA)4-CONH2 and
Ac-(IEIK)3I-CONH2, 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)3I-CONH2 self-assembles
in a stiffer hydrogel compared with the Ac-(RADA)4-CONH2 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)4-CONH2 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.
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vivo permeation studiesAUCI-CONHdrug solutionvivo studiesself-assembling peptide sequenceCONH 2 hydrogelelectron microscopy studiesTimolol MaleateControlled Ocular Delivery24 hself-assembling peptide hydrogelsCONH 2 peptideSelf-Assembling Peptide Nanofiber Hydrogelsβ- blocker timolol maleateform hydrogelsAcrheological studiesCONH 2drug deliverydrug-loaded hydrogelsHistological studies
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