Karavasili Christina, Komnenou Anastasia, Katsamenis Orestis L, Charalampidou Glykeria, Kofidou Evangelia, Andreadis Dimitrios, Koutsopoulos Sotirios, Fatouros Dimitrios G
μ-VIS X-ray Imaging Centre, Faculty of Engineering and the Environment, University of Southampton, Southampton SO17 1BJ, United Kingdom.
Center for Biomedical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
ACS Biomater Sci Eng. 2017 Dec 11;3(12):3386-3394. doi: 10.1021/acsbiomaterials.7b00706. Epub 2017 Nov 16.
The self-assembling peptides Ac-(RADA)-CONH and Ac-(IEIK)I-CONH, 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)I-CONH self-assembles in a stiffer hydrogel compared with the Ac-(RADA)-CONH 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)-CONH 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.
在生理条件下形成水凝胶的自组装肽Ac-(RADA)-CONH和Ac-(IEIK)I-CONH被评估为β受体阻滞剂马来酸噻吗洛尔眼部给药的载体。电子显微镜研究表明，水凝胶含有纳米纤维，而流变学研究表明，与Ac-(RADA)-CONH肽相比，Ac-(IEIK)I-CONH自组装形成的水凝胶更硬。体外释放和离体渗透研究表明，药物通过角膜的释放和转运是可控的，这取决于自组装肽序列。在兔体内的研究表明，与药物溶液相比，通过Ac-(RADA)-CONH水凝胶给药后，药物浓度-时间曲线下面积（AUC）显著增加，而两种载药水凝胶滴注后均可使眼内压持续降低长达24小时。组织学研究表明，制剂应用后具有良好的眼部耐受性，这表明自组装肽水凝胶是用于眼部药物持续递送的有前景的系统。
