乙衍生德克斯:一种对酸反应敏捷的可生物降解材料,用于治疗应用
Eric M Bachelder1, Tristan T Beaudette, Kyle E Broaders
1Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Journal of the American Chemical Society
|July 18, 2008
概括
修改后的德克斯产生了对pH值敏感的微粒,用于药物输送. 这些生物相容的颗粒有效地加载货物并增强疫苗反应,显示出各种应用的前景.
科学领域:
- 生物材料科学 生物材料科学
- 聚合物化学 聚合物化学
- 药物输送系统 药物输送系统
背景情况:
- 德克斯是一种生物相容,水溶性多糖.
- 目前的药物输送系统在受控释放和货物装载方面面临挑战.
- 对于特定生理环境中的向药物释放而言,对酸敏感的材料是可取的.
研究的目的:
- 开发一种新的,对酸敏感的基于德克斯的微粒系统.
- 为了评估pH值依赖的降解和货物释放动力学.
- 评估这些微粒在药物输送和疫苗应用中的潜力.
主要方法:
- 用乙烯酸部分修改德克斯以达到水不可溶性和有机溶剂可溶性.
- 使用改性德克斯制造酸敏感微粒.
- 通过单重和双重乳液技术加载疏水和疏水性货物.
- 在37°C的不同pH值 (5.0和7.4) 下对FITC-dextran释放的评估.
- 在对CD8+T细胞反应的模型疫苗申请中评估含有卵素 (OVA) 的微粒.
- 在体外细胞毒性测试以确定生物相容性.
主要成果:
- 修改后的德克斯可以轻松制备水不可溶,有机溶剂可溶的微粒.
- 微粒物表现出pH依赖的降解,在酸性pH下释放更快 (pH5.0时半衰期为10小时),而在中性pH下释放更快 (pH7.4时半衰期为~15天).
- 使用乳液技术,成功装载了疏水性和疏水性货物.
- 带有OVA的微粒显著增强了OVA衍生的呈现给CD8+T细胞 (16倍增加).
- 预先的体外测试表明,修改后的德克斯衍生物是无毒的.
结论:
- 乙改性德克斯为创建pH敏感微粒提供了一个多功能平台.
- 这些微粒提供了可控的降解和有效的货物装载,用于药物输送.
- 该系统在提高疫苗疗效方面具有显著的潜力,并且需要进一步研究治疗应用.
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