载盐酸维拉帕米碳纳米管的体外释药行为及机制研究

Study on the Release and Mechanism of Carbon Nanotubes Loaded with Verapamil Hydrochloride in vitro

目的:研究羧基化多壁碳纳米管(c-CNTs)对盐酸维拉帕米(VH)的装载及释放,并对其释药机制进行探讨,为c-CNTs作为药物缓控释载体的可行性进行评价并提供依据。方法:通过混合强酸氧化处理多壁碳纳米管(MWCNTs)制得羧基化碳纳米管(c-CNTs),利用拉曼光谱和红外光谱表征羧基的接枝、扫描电子显微镜(SEM)和高分辨透射电子显微镜(HR-TEM)对c-CNTs的微观形态进行观察;并利用HR-TEM及TEM观察盐酸维拉帕米在c-CNTs上的装载位置;考察该载药系统中药物的体外释放行为,对释放结果进行模型拟合并分析其释药机制。结果:MWCNTs通过强酸处理后成功接枝上了羧基,处理后的MWCNTs水溶性大大改善,长度由2μm左右减小至约200～300 nm,两端开口。载药及药物释放结果表明,载药量随投药量的增加而增加,当投药量较小时,药物全部装载于f-CNTs的管腔中,此时药物的释放受释放介质影响较小,其释药机制为零级释放;当投药量较大时,药物部分装载于f-CNTs的管腔中,部分位于f-CNTs的管壁,此时,药物释放受介质影响较大,随释放介质pH减小,VH释放增加,其释药机制为非Fick扩散。结论:改性后的MWCNTs可以做为药物缓释载体。可通过适当调节处方比例,达到调节药物的释放。

Objective ： The aim of this study was to load Verapamil Hydroehloride to carboxylated multi-walled carbon nanotubes （ c- CNTs） and discuss the mechanism of drug release which could act as an effective basis for c-MWNTs used as drug carriers of controlled and sustained release delivery systen~ Methods： Raw CNTs were treated with mixed strong acid to obtain c-CNTs. Raman, IR, SEM and HR-TEM were used to characterize the CNTs and investigate the loading sites for drugs. The release behavior of the drug delivery system in vitro and the release model were studied. Results： The raw CNTs were successfully grafted with carboxyl group by acid treat- ment. The water-soluble ability of e-CNTs was greatly improved. The length of e-CNTs was 200 ~ 300nm. Meanwhile, the ends of c- CNTs were opened. The results of the drug loading experiment showed that the more adding drugs, the larger loading content of drugs. Most of the drugs were loaded into the inner pores of c-CNTs when adding drugs was no more than 0. 1 as quantity as e-CNTs. As the quantity of adding drugs increased, the drugs were loaded both in the inner pores and on the out-wall of c-CNTs. The release results in vitro showed release mechanism had something with the quantity of adding drugs. Conclusion： C-CNTs can be used as carriers of sus- tained and controlled release delivery system. Ideal release behavior of drugs can be achieved by choosing appropriate formula.