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基于改性结冷胶/壳聚糖的原位形成水凝胶用于马来酸噻吗洛尔的眼部药物传递。

In situ forming hydrogels based on modified gellan gum/chitosan for ocular drug delivery of timolol maleate.

机构信息

Faculty of Chemical and Petroleum Engineering, University of Tabriz, 51666-16471 Tabriz, Iran.

Faculty of Chemical and Petroleum Engineering, University of Tabriz, 51666-16471 Tabriz, Iran.

出版信息

Int J Biol Macromol. 2024 Oct;278(Pt 4):135071. doi: 10.1016/j.ijbiomac.2024.135071. Epub 2024 Aug 24.

Abstract

In situ forming hydrogels are suitable candidates for increasing drug residence time in ocular drug delivery. In this study, gellan gum (GG) was oxidized to form aldehyde groups and in situ gelling hydrogels were synthesized based on a Schiff-base reaction between oxidized GG (OGG) and chitosan (CS) in the presence of β-glycerophosphate. The effect of OGG and CS concentration on the physical and chemical properties of the resulting hydrogels was investigated. The FT-IR spectroscopy confirmed the chemical modification of OGG as well as the functional groups of the prepared hydrogels. The scanning electron microscope (SEM) revealed the highly porous structure of hydrogels. The obtained hydrogels indicated a high swelling degree and degradability. Also, the rheological studies demonstrated self-healing behavior, shear thinning, thixotropy, and mucoadhesion properties for the developed hydrogels. The results of in vitro and ex vivo studies showed that the timolol-loaded hydrogel with a higher amount of OGG has a higher release rate. Moreover, the MTT cytotoxicity test on bone marrow mesenchymal stem cells (BMSCs) confirmed that developed hydrogels are not toxic. The obtained results revealed that the developed hydrogels can be a desirable choice for the ocular drug delivery of timolol in the treatment of glaucoma.

摘要

原位形成水凝胶是增加眼部药物输送中药物停留时间的合适候选物。在这项研究中,通过氧化凝胶多糖(GG)形成醛基,并在β-甘油磷酸存在下,通过氧化 GG(OGG)和壳聚糖(CS)之间的席夫碱反应合成原位凝胶水凝胶。研究了 OGG 和 CS 浓度对所得水凝胶的物理化学性质的影响。傅里叶变换红外光谱(FT-IR)证实了 OGG 的化学修饰以及所制备水凝胶的官能团。扫描电子显微镜(SEM)显示了水凝胶的高度多孔结构。所得水凝胶具有高溶胀度和可降解性。此外,流变学研究表明,所开发的水凝胶具有自修复行为、剪切变稀、触变和粘膜粘附特性。体外和体内研究的结果表明,含有更多 OGG 的噻吗洛尔负载水凝胶具有更高的释放速率。此外,骨髓间充质干细胞(BMSCs)的 MTT 细胞毒性试验证实,所开发的水凝胶没有毒性。研究结果表明,所开发的水凝胶可作为治疗青光眼时噻吗洛尔眼部药物输送的理想选择。

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