Active drug encapsulation and release kinetics from hydrogel-in-liposome nanoparticles.
Active drug encapsulation and release kinetics from hydrogel-in-liposome nanoparticles.
复制标题
脂质体纳米粒子水凝胶的活性药物封装和释放动力学。
DOI：
10.1016/j.jcis.2013.05.081
复制
发表时间：
2013
影响因子：
9.9
通讯作者：
Xiong,MayP
中科院分区：
文献类型：
--
作者：
Wang,Yan;Tu,Sheng;Pinchuk,AnatolyN;Xiong,MayP
在此，我们首次证明使用脂质体纳米颗粒水凝胶（lipogels）作为一种有前途的药物递送载体，用于主动封装抗癌药物 17-DMAPG（一种格尔德霉素（GA）衍生物）。选择该模型药物是因为与母体 GA (<0.01 mg/ml) 相比，其水溶性更高 (4.6 mg/ml)，并且存在在低 pH 值下容易质子化的叔胺。在脂质凝胶的设计中，通过紫外线引发的 DEAP 活化以及 AA 和 BA 的聚合，在脂质体内部形成 PAA 水凝胶核心。我们在这里证明了药物和凝胶之间的静电相互作用对于 17-DMAPG 的主动封装和持续释放至关重要。我们发现通过控制pH、温度和孵育时间可以获得最佳加载条件（加载效率为88%）。脂质凝胶可实现与外部溶液 pH 值无关的显着持续药物释放（约 54 小时至 50% 药物释放），并证实脂质双层在凝胶核心存在的情况下是完整的。体外细胞培养研究表明，在测试的最高浓度（相当于约 0.4 mg/ml 材料）下，脂质凝胶不会对细胞产生细胞毒性。
Herein, we demonstrate for the first time the use of hydrogel-in-liposome nanoparticles (lipogels) as a promising drug delivery vehicle for the active encapsulation of the anticancer drug 17-DMAPG, a geldanamycin (GA) derivative. This model drug was chosen due to its improved aqueous solubility (4.6 mg/ml) compared to the parent GA (<0.01 mg/ml), and presence of a tertiary amine which readily protonates at low pH. For the design of lipogels, a PAA hydrogel core was formed inside liposomes through UV-initiated DEAP activation and polymerization of AA and BA. We have demonstrated here that electrostatic interactions between drug and gel are critical for active encapsulation and sustained release of 17-DMAPG. We found that optimal loading conditions could be obtained (88% loading efficiency) through control of pH, temperature and incubation time. Dramatic sustained drug release from lipogels was achieved independent of the external solution pH (ca. 54 h to 50% drug release) and confirmed that the lipid bilayer was intact in the presence of the gel core.In vitrocell culture studies revealed that at the highest concentration tested, which corresponded to approximately 0.4 mg/ml of material, lipogels did not exert cytotoxicity to cells.