基于碳纳米角的荧光标记载药体系的构建、表征及体外释放

Preparation,characterization and in vitro release behavior of a fl uorescencelabeled drug delivery system based on carbon nanohorns

目的考察碳纳米角(CNHox)经不同浓度壳聚糖(CS)修饰后在水和磷酸缓冲溶液(PBS)中的分散性;构建以CNHox为载体装载多烯紫杉醇(DTX)并通过CS连接CdTe量子点荧光探针的载药体系;考察载药体系体外药物释放行为。方法测定经不同浓度CS修饰的CNHox在水中和PBS中的zeta电位,静置观察分散液的聚沉情况;饱和溶液结晶法装载DTX,热重法测定载药量;以EDC、NHS为交联剂共价连接CdTe量子点与CS,修饰到载有DTX的CNHox表面,构建新型荧光标记抗肿瘤载药体系,对该载药体系进行系列表征;考察药物体外溶出情况,高效液相色谱法测定溶出DTX的含量,并绘制体外释放曲线。结果 CS浓度达到2.50mg·mL-1时,CNHox在PBS中的分散性良好;CNHox装载DTX载药量可以达到1.170 mg·mg-1;载药体系成功标记荧光量子点,且在PBS中的分散性良好;体外累积药物释放量为54.8%,释放曲线有明显缓释行为。结论 CS修饰可提高CNHox在盐溶液中的分散性;载药体系具有较高载药量;量子点成功标记载药体系,为该载药体系的体外示踪研究奠定基础;该载药体系的体外释放试验证实具有缓释效果。

Objective To modify oxidated carbon nanohorns（CNHox） with various concentrations of chitosan（CS） to improve the dispersity of CNHox in deionized water and PBS, to assemble a novel drug delivery system（DDS） consisting of CNHox, docetaxel and CdTe quantum dots（QDs）, and to study the drug in vitro release behavior of the DDS. Methods Zeta potential values of CNHox modified by CS were determined and the times of coagulation were monitored. A saturated solution crystallization method was adopted to load docetaxel（DTX） onto CNHox, and the loading rate of DTX was measured with thermogravimetric analysis. The CS was conjugated with CdTe QDs covalently followed by modifying CNHox on the surface to fi nish the preparation of the DDS, which was characterized with methods of fl uorescense spectrum, transmission electron microscope（TEM）, zeta potential analysis and inverted fluorescence microscope imaging. The release of DTX from the DDS was evaluated by dialysis bag immersed in the PBS, and an HPLC method was established to measure the amount of DTX. Results CNHox had a good dispersity in the PBS when they were modifi ed by CS at 2.50 mg·mL- 1. A high drug loading rate of 1.170 mg·mL- 1（DTX to CNHox） was obtained. The DDS was labeled by CdTe QDs and well dispersed in the PBS; 54.8% DTX loaded onto CNHox was released in 48 h in vitro, showing a slow release. Conclusion Dispersity of CNHox in the PBS is improved after CS modifi cation. DTX is loaded onto CNHox at a high rate. The DDS was labeled with CdTe QDs, making in vitro cell imaging possible. The DDS also shows slow release of docetaxel, indicating a potential drug form.