Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
J Biomater Appl. 2012 Nov;27(4):391-402. doi: 10.1177/0885328211406563. Epub 2011 Jul 12.
The purpose of this study was to evaluate the feasibility of in situ thermosensitive hydrogel based on chitosan in combination with disodium α-d-Glucose 1-phosphate (DGP) for ocular drug delivery system. Aqueous solution of chitosan/DGP underwent sol-gel transition as temperature increased which was flowing sol at room temperature and then turned into non-flowing hydrogel at physiological temperature. The properties of gels were characterized regarding gelation time, gelation temperature, and morphology. The sol-to-gel phase transition behaviors were affected by the concentrations of chitosan, DGP and the model drug levocetirizine dihydrochloride (LD). The developed hydrogel presented a characteristic of a rapid release at the initial period followed by a sustained release and remarkably enhanced the cornea penetration of LD. The results of ocular irritation demonstrated the excellent ocular tolerance of the hydrogel. The ocular residence time for the hydrogel was significantly prolonged compared with eye drops. The drug-loaded hydrogel produced more effective anti-allergic conjunctivitis effects compared with LD aqueous solution. These results showed that the chitosan/DGP thermosensitive hydrogel could be used as an ideal ocular drug delivery system in terms of the suitable sol-gel transition temperature, mild pH environment in the hydrogel as well as the organic solvent free.
本研究旨在评估壳聚糖与二磷酸葡萄糖二钠（DGP）原位温敏水凝胶用于眼部药物传递系统的可行性。壳聚糖/DGP 的水溶液在温度升高时发生溶胶-凝胶转变，在室温下为流动溶胶，在生理温度下转变为不流动水凝胶。凝胶的性质通过凝胶时间、凝胶温度和形态进行了表征。溶胶-凝胶相变行为受到壳聚糖、DGP 和模型药物左西替利嗪二盐酸盐（LD）浓度的影响。所开发的水凝胶呈现出初始快速释放，随后持续释放的特征，并显著增强了 LD 的角膜穿透性。眼部刺激性研究结果表明水凝胶具有良好的眼部耐受性。与滴眼液相比，水凝胶的眼部滞留时间明显延长。与 LD 水溶液相比，载药水凝胶产生了更有效的抗过敏性结膜炎作用。这些结果表明，壳聚糖/DGP 温敏水凝胶可以作为一种理想的眼部药物传递系统，具有合适的溶胶-凝胶转变温度、水凝胶中温和的 pH 环境以及无有机溶剂。
