载阿霉素海藻酸钠纳米粒的制备及体外释药行为研究

Preparation of doxorubicin-loading sodium alginate nanoparticles and their in vitro release

目的以海藻酸钠(sodium alginate,ALG)为材料,制备载阿霉素海藻酸钠纳米粒(doxorubicin loading nanoparticles,DOX-ALG-NPs),并对其载药、释药特性进行研究。方法采用微乳-离子交联法制备空白海藻酸钠纳米粒(ALG-NPs),以吸附法载药制备阿霉素海藻酸钠纳米粒(DOX-ALG-NPs)。采用效应面法对ALG-NPs的处方进行优化,并考察ALG-NPs悬液浓度、药载比、孵育时间及孵育温度对ALG-NPs载药性能的影响。对DOX-ALG-NPs的基本性质及体外释药行为进行考察。结果成功制备了粒径为(262.0±4.5)nm的ALG-NPs及粒径为(159.8±8.1)nm、包封率及载药量分别为(94.2±0.5)%和(19.05±0.085)%的DOX-ALG-NPs。与原料药DOX相比,DOX-ALG-NPs在生理盐水与PBS(pH=7.4)中均呈现明显的缓释作用,在生理盐水和PBS中2 h与5 h时分别释放药物(38.1±1.5)%与(55.5±1.1)%、(40.0±1.8)%与(48.1±2.5)%,24 h时分别释放(73.1±3.2)%、(60.3±3.4)%。结论所制备的DOX-ALG-NPs形态圆整,粒径小且分布均匀,包封率及载药量较高,具有缓释性能,有望用作抗癌药物传递系统。

Objective To prepare doxorubicin-loading sodium alginate nanoparticles （DOX-ALG-NPs） with sodium alginate as the carrier material and to investigate the drug loading capacity and release behavior in vitro. Methods Blank ALG-NPs were prepared by microemulsion-ionotropic gelation method, and DOX was loaded by adsorption. Response surface method was used to optimize the formulation of ALG-NPs. The influence of ALG-NP concentration, ratio of DOX to ALG, incubation time and incubation temperature on drug loading capacity of ALG-NPs was determined. The basic properties and drug release behaviors in vitro were characterized. Results The optimized ALG-NPs and DOX-ALG-NPs were round with a mean size of （262.0 ±4.5） nm and （159.8±8.1） nm, respectively. The entrapment efficiency and drug loading rate of DOX-ALG-NPs were （94.2±0.5）% and （19.05 ±0.085） %, respectively. Compared with DOX, the release behaviors of DOX-ALG-NPs in both normal saline and PBS （pH = 7. 4） demonstrated typical sustained release. In the normal saline the accumulative drug release percentage （Q%） at 2 h and 5 h was （38.1 ±1.5） % and （55.5 ±1.1） %, while in the PBS was （40.0±1.8） % and （48.1± 2.5） %. At 24 h, the Q% was （73.1± 3.2） % and （60.3 ±3.4） % in the normal saline and the PBS, respectively. Conclusion The optimized DOX-ALG-NPs are round particles with small size and narrow distribution. The DOX-ALG-NPs have high entrapment efficiency, drug loading rate and sustained release as well, which can be used in an anti-cancer drug delivery system.