Department of Ophthalmology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Int J Pharm. 2011 Jun 15;411(1-2):69-77. doi: 10.1016/j.ijpharm.2011.03.042. Epub 2011 Mar 29.
Conventional eye drops can result in poor drug bioavailability due to the unique ocular anatomy and physiology. Ion-activated in situ gelling systems are able to crosslink with cations present in the tear fluid, therefore forming a gel on the ocular surface, which results in prolonged corneal contact time. The present study compared a number of anionic polysaccharides (gellan gum, xanthan gum, carrageenan and alginate) to an uncharged (HPMC) and a positively charged (chitosan) polymer system with emphasis on the gelling behaviour, rheological and textural properties, gel microstructure, contact angle and in vitro release characteristics. All systems exhibited physically entangled polymer networks that were able to disentangle upon shear stress and significantly prolonged the in vitro release of a model hydrophilic drug compared to a solution. While systems based on HPMC and chitosan showed no structural changes upon addition of cations, formulations based on gellan gum and carrageenan demonstrated a remarkable increase in viscosity, pseudoplasticity and hardness upon addition of Ca(2+) and K(+) respectively. This renders them favourable for ocular use as they would gel once in contact with the cations of the tear fluid, thus reducing nasolacrimal drainage, but would thin upon shearing, preventing ocular irritation and therefore induced lacrimation.
由于眼部独特的解剖结构和生理特性，常规眼药水的药物生物利用度较差。离子型原位凝胶系统能够与泪液中的阳离子交联，从而在眼表面形成凝胶，延长角膜接触时间。本研究比较了几种阴离子多糖（结冷胶、黄原胶、卡拉胶和海藻酸钠）与非带电（HPMC）和带正电荷（壳聚糖）聚合物系统，重点研究了凝胶行为、流变学和质构特性、凝胶微观结构、接触角和体外释放特性。所有系统都表现出物理缠结的聚合物网络，在剪切应力下能够解缠，并显著延长模型亲水性药物的体外释放。虽然基于 HPMC 和壳聚糖的系统在添加阳离子后没有结构变化，但基于结冷胶和卡拉胶的制剂在添加 Ca(2+)和 K(+)后分别表现出粘度、假塑性和硬度的显著增加。这使得它们适合眼部使用，因为它们一旦与泪液中的阳离子接触就会形成凝胶，从而减少鼻泪管引流，但在剪切时会变薄，防止眼部刺激和因此引起的流泪。
