下一代精密聚合物可用于模块化药物输送,优化连接体受体静态测量
Raghu Ganugula1, Meenakshi Arora1, Prabhjot Saini1
1Department of Pharmaceutical Sciences, College of Pharmacy, Texas A&M University , TAMU Mailstop 1114, College Station, Texas 77843, United States.
Journal of the American Chemical Society
|April 11, 2017
概括
研究人员开发了新型精密聚纳米系统 (P2N) 以优化药物输送. 这些P2N增强细胞吸收,并通过控制联体受体相互作用来实现个性化剂量.
科学领域:
- 生物材料科学
- 纳米技术
- 提供药物
背景情况:
- 通过受体介导的药物输送需要精确的联体受体静态度测量,而传统的聚合物如PLA和PLGA是有限的.
- 现有的药物输送系统缺乏优化纳米颗粒表面连接体密度的灵活性.
研究的目的:
- 合成和描述一个新的精密聚合物 (P2s) 平台,使可调节的碳基功能化.
- 开发纳米系统 (P2N) 具有受控的甘博基酸 (GA) 结合,以优化药物输送中的联体受体相互作用.
- 评估这些P2N的细胞吸收,细胞内流通和体内性能.
主要方法:
- 合成了12种基于PLA-PEG的精密聚合物 (P2s) 的变化,其碳酸基区间不同.
- 将甘酸 (GA) 与P2s结合,以产生P2s-GA,并用光P2s制成纳米系统 (P2N).
- 在caco-2细胞中评估P2N细胞吸收,并与PLGA-GA纳米系统进行比较.
- 使用活细胞成像进行细胞内贩运的调查.
- 在肠道组织中评估P2N转移素受体 (TfR) 的同位化.
- 在体内使用循环素 (CsA) 装载的P2N来评估药物释放特征的研究.
主要成果:
- P2s平台允许控制GA结合,创建具有可调的表面GA密度 (<150 nm) 的P2N.
- 与传统的PLGA- GA纳米系统相比,P2Ns在caco-2细胞中显示出更高的细胞吸收率.
- 细胞吸收与表面GA密度比例增加至75%,表明受体和率为100%.
- 已证实内细胞通路参与P2N细胞吸收.
- 即使在TfR被阻断的情况下,P2Ns在肠道组织中表现出TfR局部化.
- 在体内研究显示,药物释放的模块化特征取决于表面GA密度.
结论:
- 开发的精密聚纳米系统 (P2N) 为优化药物输送中的联体受体静态度提供了多功能平台.
- P2N 呈现出增强的细胞吸收和受控的药物释放,为个性化医疗方法铺平了道路.
- 这种平台有可能为各种治疗应用开发量身定制的药物输送方案.
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