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基于热敏壳聚糖-明胶的水凝胶持续递送拉坦前列素以控制高眼压症。

Sustained delivery of latanoprost by thermosensitive chitosan-gelatin-based hydrogel for controlling ocular hypertension.

作者信息

Cheng Yung-Hsin, Hung Kuo-Hsuan, Tsai Tung-Hu, Lee Chia-Jung, Ku Ruy-Yu, Chiu Allen Wen-Hsiang, Chiou Shih-Hwa, Liu Catherine Jui-Ling

机构信息

Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.

Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Ophthalmology, National Yang-Ming University Hospital, I-Lan, Taiwan.

出版信息

Acta Biomater. 2014 Oct;10(10):4360-6. doi: 10.1016/j.actbio.2014.05.031. Epub 2014 Jun 7.

DOI:10.1016/j.actbio.2014.05.031
PMID:24914827
Abstract

Glaucoma is an irreversible ocular disease that may lead to progressive visual field loss and eventually to blindness with inadequately controlled intraocular pressure (IOP). Latanoprost is one of the most potent ocular hypotensive compounds, the current first-line therapy in glaucoma. However, the daily instillation required for efficacy and undesirable side-effects are major causes of treatment adherence failure and persistence in glaucoma therapy. In the present study, we developed an injectable thermosensitive chitosan/gelatin/glycerol phosphate (C/G/GP) hydrogel as a sustained-release system of latanoprost for glaucoma treatment. The latanoprost-loaded C/G/GP hydrogel can gel within 1min at 37°C. The results show a sustained release of latanoprost from C/G/GP hydrogel in vitro and in vivo. The latanoprost-loaded C/G/GP hydrogel showed a good in vitro and in vivo biocompatibility. A rabbit model of glaucoma was established by intravitreal injection of triamcinolone acetonide. After a single subconjunctival injection of latanoprost-loaded C/G/GP hydrogel, IOP was significantly decreased within 8days and then remained at a normal level. The results of the study suggest that latanoprost-loaded C/G/GP hydrogel may have a potential application in glaucoma therapy.

摘要

青光眼是一种不可逆的眼部疾病,若眼内压(IOP)控制不当,可能导致进行性视野缺损,最终失明。拉坦前列素是最有效的降眼压药物之一,是目前青光眼的一线治疗药物。然而,为达到疗效所需的每日滴眼给药以及不良副作用是青光眼治疗中导致治疗依从性差和持续性不佳的主要原因。在本研究中,我们开发了一种可注射的热敏壳聚糖/明胶/甘油磷酸酯(C/G/GP)水凝胶,作为拉坦前列素用于青光眼治疗的缓释系统。负载拉坦前列素的C/G/GP水凝胶在37°C下1分钟内即可凝胶化。结果表明,拉坦前列素从C/G/GP水凝胶中在体外和体内均有持续释放。负载拉坦前列素的C/G/GP水凝胶表现出良好的体外和体内生物相容性。通过玻璃体内注射曲安奈德建立兔青光眼模型。单次结膜下注射负载拉坦前列素的C/G/GP水凝胶后,眼内压在8天内显著降低,然后维持在正常水平。研究结果表明,负载拉坦前列素的C/G/GP水凝胶在青光眼治疗中可能具有潜在应用价值。

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