碳酸钙复合纳米载体的制备及体外评价

Preparation and in vitro Evaluation of Calcium Carbonate Composite Nanocarriers

采用复合模板法制备了由壳聚糖-聚甲基丙烯酸共聚物、碳酸钙组成的pH响应型核壳结构复合碳酸钙空腔纳米载体,并以盐酸多柔比星为模型药,评价了该载体的体外释放和抗肿瘤活性。结果显示,该空白纳米载体呈类球形,平均粒径为(345.8±10.4)nm,多分散系数为0.214±0.035,ζ电位为(-48.5±2.1)mV。调节至pH 8.0可使该空白纳米载体吸附药物,最终得到载药量和包封率为(17.4±0.3)%和(78.5±3.2)%的载药纳米载体。体外释放试验中载药纳米载体表现出优越的pH响应性,即在pH 7.4介质中24 h累积释放率低于10%,在pH 6.8和pH 5.5介质中则可达到40%和70%。HepG2细胞毒性试验表明,共聚物、空白纳米载体均无明显细胞毒性,而载药纳米载体对HepG2细胞有显著的浓度依赖性抑制作用。结果表明这种壳核结构纳米载体有作为治疗肝癌的pH敏感载体的应用前景。

The pH-responsive core-shell composite calcium carbonate hollow nanocarriers composed of chitosan-poly(methylacrylic acid)copolymer and calcium carbonate were developed by the composite template method in the paper.Furtherly,the drug-loaded nanoparticles were prepared with doxorubicin hydrochloride as model drug.The in vitro release and antitumor activity were also investigated.The results showed that the average particle size,polydispersity index andζpotential of the blank nanocarriers having a spherical shape with core-shell nanostructure were(345.8±10.4)nm,0.214±0.035 and(-48.5±2.1)mV,respectively.The blank nanocarriers could incorporate drugs into the cores by adjusting the pH of medium to 8.0.Finally,the drug-loaded nanoparticles were obtained with a high drug loading of(17.4±0.3)%and an encapsulation efficiency of(78.5±3.2)%.In in vitro release test,the product showed a great pH responsibility.The cumulative release at 24 h in pH 7.4 medium was below 10%,while in pH 6.8 and pH 5.5 media were 40%and 70%,respectively.There were no obvious cytotoxicities of the copolymer and the blank nanocarriers against HepG2 cells,while the drug-loaded nanoparticles showed a significant inhibition effect in a concentration-dependent manner.The results indicated that the shell-core nanocarriers had application prospects for liver cancer treatment as pH-sensitive carriers.