期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 3, 期 12, 页码 3386-3394出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.7b00706
关键词
self-assembling peptide; ocular delivery; timolol maleate; glaucoma; intraocular pressure; pharmacokinetics
资金
- Research Committee of Aristotle University of Thessaloniki [90633]
The self-assembling peptides Ac-(RADA)(4)CONH2 and Ac-(IEIK)(3)I-CONH2r, which form hydrogels in physiological conditions, were evaluated as carriers for ocular delivery of the beta-blocker timolol maleate. Electron microscopy studies revealed that hydrogels contain nanofibers, whereas rheological studies showed that the Ac-(IEIK)(3)I-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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