The 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.

中文翻译：

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自组装肽纳米纤维水凝胶可控制马来酸替莫洛尔的眼部递送

评价了在生理条件下形成水凝胶的自组装肽Ac-（RADA）₄ -CONH ₂和Ac-（IEIK）₃ I-CONH ₂作为β-阻滞剂马来酸替莫洛尔的眼用载体。电子显微镜研究表明水凝胶包含纳米纤维，而流变学研究表明，与Ac-（RADA）₄ -CONH ₂相比，Ac-（IEIK）₃ I-CONH ₂在更硬的水凝胶中自组装。肽。体外释放和离体渗透研究表明药物通过角膜的受控释放和运输，这取决于自组装肽序列。兔体内研究显示，与药物溶液相比，通过Ac-（RADA）₄ -CONH ₂水凝胶给药后，浓度-时间曲线（AUC）下的面积显着增加，而眼内压持续降低两种载药的水凝胶均在滴注后长达24小时。组织学研究表明，使用该制剂后具有良好的眼耐受性，表明自组装肽水凝胶是持续眼药递送的有前途的系统。