合成高分子基温敏水凝胶在眼病治疗中的研究进展

由于眼部存在角膜/结膜屏障、血-房水屏障和血-视网膜屏障等,有效的眼部给药依然面临巨大挑战.近年来,温敏水凝胶在眼部给药领域受到了广泛关注.在室温下,温敏水凝胶材料呈液态,便于以局部滴加或玻璃体内注射的方式给药;当与眼部接触升温并超过其临界成胶温度时,能以物理交联的方式快速凝胶化,从而实现原位缓释给药,提高药物生物利用度.在众多温敏水凝胶材料中,合成高分子具有材料和功能多样化等优势,其中较常见的为泊洛沙姆、聚乙二醇/聚酯和聚(N-异丙基丙烯酰胺).本综述首先介绍了以上3类合成高分子基温敏水凝胶材料的制备方法和成胶特性.然后,围绕眼部给药存在的难点,探讨这些温敏水凝胶在治疗角膜病、干眼症、青光眼和眼部炎症等各种眼病中的相关研究进展.最后,我们比较了这3种水凝胶在使用性能上的优缺点,并对未来眼科温敏水凝胶的材料设计提出了设想和展望.

The Progress in Thermogels Based on Synthetic Polymers for Treating Ophthalmic Diseases

Due to the presence of several physiological barriers,including corneal barrier,blood-aqueous humor barrier and blood-retinal barrier,efficient drug delivery remains a huge challenge in the treatment of ocular diseases.In recent years,in situ forming thermogels have emerged as ideal drug delivery systems(DDSs)with sustained-release feature,receiving extensive attention in the field of ocular drug delivery.At room temperature,thermogels in liquid form can be easily administrated by topical instillation or intravitreal injection.Once in contact with the eye,physical crosslinking induced sol-gel transition will take place in-situ when the liquid temperature exceeds the critical gelation temperature.Thus,drug retention time can be prolonged and drugs can be continuously released for a longer term to enhance drug bioavailability.Benefiting from the advantages of synthetic polymers in terms of material diversity and versatility,thermogels based on synthetic polymers are the current hotspot in the research of temperature-induced hydrogels.Poloxamer,polyethylene glycol/polyester and poly(N-isopropylacrylamide)are the three most common synthetic thermo-gelling polymers.In this review,we will first introduce preparation methods and gel-forming properties of these synthetic polymer-based thermogels.Then,the research progress of the application of synthetic thermogels in the treatment of ophthalmic diseases,including corneal disorders,dry eye syndrome,glaucoma,ocular inflammation,and others,is mainly discussed.Last but not the least,the advantages and disadvantages of these three thermogels are compared,and future perspectives on the design of novel synthetic thermogels for ophthalmic applications are suggested.