Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye hospital, Wenzhou Medical College, 270 Xueyuan Road, Wenzhou 325027, China.
Int J Biol Macromol. 2013 Sep;60:272-6. doi: 10.1016/j.ijbiomac.2013.05.034. Epub 2013 Jun 5.
Avastin(®) was the first choice drug for the treatment of age related macular degeneration (AMD) and proliferative diabetic retinopathy in clinic. Due to its short half-time in intraocular, it was required repeat administration. In this paper, an in situ injectable polysaccharides cross-linked hydrogel was developed for potential ocular drug delivery of avastin. The polysaccharide cross-linked hydrogel was first synthesized by simple mixing of glycol chitosan and oxidized alginate aqueous solution, and then characterized by scanning electron microscopy (SEM) and rheometer. In vitro degradation test indicated that the degradation rate of hydrogels could be controlled by the varying the content of oxidized alginate in hydrogels. In vitro release study showed that the encapsulated avastin had an initial burst release at early stage (within 4 h) followed by a sustained release manner in period of 3 days. With the increase of oxidized alginate concentration in the hydrogel, the release rate of avastin from hydrogels declined accordingly. Meanwhile, the structure stability of avastin released from hydrogels at specific time intervals did not show apparent changes as compared with native avastin based on the analysis of SDS-polyacrylamide gel electrophoresis (SDS-PAEG). As a result, the developed in situ injectable polysaccharides cross-linked hydrogel with controllable degradation rate and drug release might be a versatile carrier for avastin to apply in ocular drug delivery.
贝伐单抗（®）是治疗年龄相关性黄斑变性（AMD）和增生性糖尿病视网膜病变的临床首选药物。由于其在眼内的半衰期较短，需要重复给药。本文开发了一种原位可注射多糖交联水凝胶，用于潜在的眼部阿瓦斯汀给药。多糖交联水凝胶首先通过简单混合壳聚糖和氧化海藻酸钠水溶液合成，然后通过扫描电子显微镜（SEM）和流变仪进行表征。体外降解试验表明，水凝胶的降解速率可以通过改变水凝胶中氧化海藻酸钠的含量来控制。体外释放研究表明，包封的贝伐单抗在早期（4 小时内）有初始突释，随后在 3 天内呈持续释放方式。随着水凝胶中氧化海藻酸钠浓度的增加，贝伐单抗从水凝胶中的释放速率相应降低。同时，根据十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAEG）分析，与天然贝伐单抗相比，在特定时间间隔从水凝胶中释放的贝伐单抗的结构稳定性没有明显变化。因此，开发的具有可控降解率和药物释放的原位可注射多糖交联水凝胶可能是阿瓦斯汀在眼部药物输送中的一种多功能载体。
