替莫唑胺酯纳米粒的制备及抗脑胶质瘤活性研究

Preparation and Anti-glioma Activity of Temozolomide Ester Loaded Nanoparticles

制备并优化替莫唑胺辛酯纳米粒(TOE-NPs),对其进行体外表征及抗脑胶质瘤效果考察.采用Box-Behnken响应面法优化替莫唑胺辛酯纳米粒处方;对采用最优处方制备的纳米粒的粒径、包封率、载药量、体外药物释放特性等进行评价,以大鼠脑胶质瘤细胞(C6)为模型细胞考察抗胶质瘤效果.纳米粒最优处方为:有机相与水相体积比(1∶3.3),聚乳酸-羟基乙酸共聚物(PLGA)质量浓度8.80 mg/mL,理论载药量17.77%,所制备的替莫唑胺辛酯纳米粒粒径为136.2±3.4 nm,包封率为(93.29±1.93)%,120 h累计释放率为(88.13±2.39)%,MTT结果显示替莫唑胺辛酯纳米粒对C6细胞的生长抑制活性强于替莫唑胺纳米粒(IC 50,28.16μmol/L和169.12μmol/L,P<0.01).所优选的纳米粒处方合理可行,替莫唑胺辛酯纳米粒有明显的缓释特性和较强的体外抗胶质瘤活性.

Temozolomide octyl ester nanoparticles(TOE-NPs)are prepared and optimized for in vitro characterization and anti-glioma effects.The Box-Behnken response surface method is used to optimize the formulation of temozolomide octyl ester nanoparticles.The particle size,encapsulation efficiency,drug loading and drug release characteristics of nanoparticles prepared by the optimal formulation are evaluated.Rat glioma cells(C6)are used as model cells to investigate the anti-glioma effect.The optimal formulation of nanoparticles is as follows:oil-water ratio is 1:3.3,PLGA concentration is 8.80 mg/mL,theoretical drug loading is 17.77%,the particle size is 136.2±3.4 nm,the encapsulation efficiency is(93.29±1.93)%,and the cumulative release rate at 120 h is(88.13±2.39)%.The MTT results show that temozolomide octyl ester nanoparticles have stronger growth inhibitory activity against C6 cells than temozolomide nanoparticles(IC 50,28.16μmol/L vs 169.12μmol/L,P<0.01).The preferred nanoparticle formulation is reasonable and feasible,and the temozolomide octyl ester nanoparticles have obvious sustained release properties and strong anti-glioma activity in vitro.