地塞米松纳米胶束的制备及体外抗肿瘤作用研究

摘要

目的：制备地塞米松（Dex）纳米胶束（简称Dex胶束），并研究其体外抗肿瘤作用。方法：以γ-聚谷氨酸（γ-PGA）为载体、二甲基亚砜为有机溶剂，采用透析法制备Dex胶束；观察并检测其形态、粒径、Zeta电位、多分散系数（PDI）、临界胶束浓度（CMC）、载药量、包封率；比较pH 5.5、7.4条件下Dex胶束和Dex的体外释药情况；比较0.05、0.1、0.2、0.5、1.0μmol/ml的Dex、γ-PGA、Dex胶束和泼尼松龙（阳性对照）对人肺腺癌A549细胞存活率的影响，比较A549细胞在4、37℃下对0.5μmol/ml的Dex胶束和Dex的摄取量。结果：所制备Dex胶束呈圆球形、形态规则，粒径为（76.25±3.74）nm，Zeta电位为5.0 mV，PDI为0.163±0.38，CMC为7.609μg/ml，载药量为（9.56±0.92）％，包封率为（89.25±1.36）％；与Dex比较，Dex胶束在pH 5.5、7.4条件下释药时间延长；在0.05～0.2μmol/ml范围内，游离Dex、γ-PGA、Dex胶束和泼尼松龙对细胞存活率的影响差异无统计学意义（P＞0.05）；在0.5、1.0μmol/ml时，Dex胶束作用下细胞存活率明显低于游离Dex或泼尼松龙作用（P＜0.05）。4℃下，细胞对Dex胶束和Dex的摄取量差异无统计学意义（P＞0.05）；37℃下，细胞对Dex胶束的摄取量明显高于游离Dex和4℃下的游离Dex、Dex胶束（P＜0.05）。结论：所制备的Dex胶束能延长Dex的释药时间，降低A549细胞的存活率和细胞的摄取效率。%OBJECTIVE:To prepare Dexamethasone(Dex)nano-micelles(called Dex micelles for short),and to study its in vitro anti-tumor effect. METHODS:Using γ-PGA as carrier,DMSO as organic solvent,Dex micelles were prepared by dialysis method. The morphology,particle size,Zeta potential,PDI,CMC,drug-loading amount and entrapment efficiency (EE) of mi-celle were observed and detected. Drug release of Dex micelles and Dex were compared under pH 5.5,7.4. The effects of free Dex,γ-PGA,Dex micelles and prednisolone(positive control)(0.05,0.1,0.2,0.5,1.0 μmol/ml)on the survival rate of human lung adenocarcinoma A549 cells were compared. The uptake amount of A549 cells to 0.5 μmol/ml Dex micelles and free Dex were compared at 4,37 ℃. RESULTS:Prepared Dex micelles were spheroidal and completely round with particle size of(76.25±3.74) nm,Zeta potential of 5.0 mV,PDI of 0.163 ± 0.38,CMC of 7.609 μg/ml,drug-loading amount of (9.56 ± 0.92)% and EE of (89.25 ± 1.36)%. Compared with free Dex,the duration of drug release for Dex micelles prolonged under pH 5.5,7.4. When the concentration ranged 0.05-0.2 μmol/ml,the effects of free Dex,γ-PGA,Dex micelles and prednisolone on cellular survival rate had no statistically significant difference(P>0.05). When the concentration was 0.5,1.0 μmol/ml,survival rate of A549 cells treat-ed with Dex micelles was significantly lower than that treated with free Dex or prednisolone (P<0.05). At 4 ℃,the uptake amount of A549 cells to Dex micelles and free Dex had no statistically significant difference (P>0.05). At 37 ℃,the uptake amount of A549 cells to Dex micelles was significantly higher than that of cells to free Dex,and that of A549 cells to Dex micelles and free Dex at 4 ℃. CONCLUSIONS:Prepared Dex micelles can prolong the duration of drug release of Dex,and decrease the survival rate of A549 cells and cellular uptake efficacy.