透明质酸修饰的空腔靶向纳米载体制备及其体内外性能评价

目的： 制备具有pH响应性的透明质酸衍生物修饰的主动靶向载药空腔纳米球载体，并进行相关性能测定。方法： 采用One-pot法制备空腔碳酸钙纳米球，并用透明质酸与壳聚糖的偶联物进行修饰，得到具有pH响应性的靶向给药载体；以阿霉素作为模型药物，对载体的粒径及Zeta电位、包封率、载药量及体外释放进行考察；以人肝癌HepG2细胞，通过MTT实验进行细胞毒性验证；以H22荷瘤小鼠为模型验证载体在体内及肿瘤部位的靶向性作用。结果： 所制备的靶向给药载体呈球状，平均粒径（376.8±12.4）nm，PDI为（0.295±0.080），Zeta电位为（-45.1±0.3）mV，包封率（80.45±2.35）%及载药量（15.65±0.25）%；体外释放显示出此载体具有良好的pH响应性，且具有明显的缓释特征；细胞毒性实验证明了此载体具有低毒性；荷瘤小鼠实验证明了此载体具有良好的肝靶向和肝肿瘤靶向能力。结论： 成功制备了透明质酸衍生物修饰的碳酸钙空腔纳米球靶向给药载体，此载体具有良好肝癌靶向治疗的能力。

Preparations and evaluations of in vitro and in vivo characteristics of hyaluronic acid-modified hollow targeted nanocarriers

OBJECTIVE To prepare a pH-responsive hyaluronic acid derivative-modified active targeting hollow nanocarrier and evaluate its relevant characteristics.METHODS The hollow calcium carbonate nanospheres were prepared by one-pot method and modified by a conjugate of hyaluronic acid and chitosan, obtaining a targeted drug delivery carrier with pH responsiveness. Particle size, Zeta potential, encapsulation efficiency, drug loading and in vitro release of carrier were examined with doxorubicin as a model drug. In vitro cytotoxicity of the carrier was assessed by MTT assay in human hepatocellular carcinoma (HepG2) cells. The effects of tumor targeting in vivo were determined with a H22 tumor-bearing murine model.RESULTS The targeted drug delivery carrier was spherical with an average particle size of (376.8±12.4) nm, a PDI of (0.295±0.080), a Zeta potential of (-45.1±0.3) mV, an encapsulation efficiency of (80.45±2.35)% and drug loading (15.65±0.25)%. The in vitro release studies showed that the carrier had good pH responsiveness and showed obvious sustained release properties. The cytotoxicity test proved that the carrier possessed low cell toxicity. The studies in tumor-bearing mice proved that the carrier has good liver targeting and hepatocellular carcinoma targeting capacity.CONCLUSION The targeted delivery carrier of calcium carbonate cavity nanospheres modified by hyaluronic acid derivatives has been successfully prepared with good potential for targeted therapy of hepatocellular carcinoma.