复合碳酸钙空腔纳米粒的制备及性能评价

Preparation and Properties Evaluation of Composite Calcium Carbonate Hollow Nanoparticles

关键词:  碳酸钙  甘草次酸  海藻酸钠  纳米粒

Key words:  CaCO₃  glycyrrhetinic acid  sodium alginate  nanoparticle

摘要:

目的 制备甘草次酸/海藻酸钠修饰碳酸钙空腔纳米粒并进行性能评价。方法 以可溶性淀粉为模板剂制备中空球状碳酸钙纳米粒（CaCO₃ nanoparticles，CaCO₃ Nps）；在非均相体系中合成了甘草次酸/海藻酸钠聚合物（glycyrrhetinic acid/sodium alginate copolymer，GA-ALG）；并以GA-ALG为壳，以中空结构的CaCO₃ Nps为核，合成了壳核结构的GA-ALG-CaCO₃ Nps。采用Malvern粒度分析仪测定纳米粒子的粒度分布和Zeta电位，并通过SEM对纳米粒的形态进行表征。应用荧光分光光度计评价载盐酸阿霉素（doxorubicin hydrochloride，DOX）纳米粒的载药量、包封率及体外释放特征。结果 GA-ALG-CaCO₃ Nps分布均一，平均粒径为（425.4±31.1）nm，PDI为0.289；Zeta电位为（-17.0±0.3）mV；其载药量为（13.06±0.51）%，包封率为（78.35±3.08）%。体外释放结果显示，纳米粒具有一定的缓释作用。肝靶向研究结果显示DOX/GA-ALG-CaCO₃ Nps的靶向效率为68.2%，远高于DOX对照组24.2%。结论 GA-ALG-CaCO₃ Nps作为新型的药物载体，具有良好的pH响应性，并能显著提高载药量，还具有明显的缓释效果及良好的肝靶向能力。

Abstract:

OBJECTIVE To prepare surface modified calcium carbonate nanoparticles with glycyrrhetinic acid/sodium alginate and to evaluate its properties. METHODS The hollow spherical calcium carbonate nanoparticles(CaCO₃ Nps) were prepared using soluble starch as organic templates. Glycyrrhetinic acid/sodium alginate copolymer(GA-ALG) was synthesized in heterogeneous system. GA-ALG-CaCO₃ Nps with shell-core structure were synthesized by using GA-ALG as shell and hollow CaCO₃ nanoparticles as core. The particle size distribution and Zeta potential of nanoparticles were measured by Malvern particle size analyzer, and the morphology of nanoparticles was characterized by SEM and TEM. The drug loading, entrapment efficiency and in vitro release characteristics of nanoparticles loaded with doxorubicin hydrochloride(DOX) was evaluated by fluorescence spectrophotometer. RESULTS The average size of GA-ALG-CaCO₃ Nps was (425.4±31.1)nm, PDI was 0.289, Zeta potential was (-17.0±0.3)mV, drug loading was (13.06±0.51)%, encapsulation efficiency was (78.35±3.08)%. In vitro release results showed that nanoparticles had a certain sustained release effect. The results of studies on liver-targeting showed that the targeting efficiency of DOX/GA-ALG-CaCO₃ Nps was 68.2%, which was much higher than the DOX control group's 24.2%. CONCLUSION As a new drug carrier, GA-ALG-CaCO₃ Nps has good pH responsiveness, can significantly increase drug loading, and has obvious sustained release effect and a better liver-targeting capacity.