Preparation, Characterization, and In Vitro pH-sensitivity Evaluation of Superparamagnetic Iron Oxide Nanoparticle-Misonidazole pH-sensitive Liposomes
Preparation, Characterization, and In Vitro pH-sensitivity Evaluation of Superparamagnetic Iron Oxide Nanoparticle-Misonidazole pH-sensitive Liposomes
复制标题
超顺磁性氧化铁纳米粒-米索硝唑pH敏感性脂质体的制备、表征及体外pH敏感性评价
DOI：
10.2174/1567201816666181114124333
复制
发表时间：
2019-01-01
影响因子：
2.4
通讯作者：
He, Mei
中科院分区：
文献类型：
--
作者：
Li, Bibo;Li, Biqiang;He, Mei
背景：咪唑(MISO)是第一种潜在的缺氧性肿瘤细胞放射增敏剂，但其外周神经毒性限制了其应用，阻碍了III期临床试验的进行。目的：开发一种含有pH敏感脂质体(SpHls)和超顺磁性氧化铁纳米粒(SPION)的靶向给药和示踪系统，以对抗MISO相关的不良反应，并实现磁共振示踪。建立了MISO和Fe的高效液相色谱和邻菲咯啉分光光度测定方法。结果：Spion-MISO和SPION对Spion-MISO-SpHls的最大包封率分别为30.2%和23.7%。MISO和SPIONS在pH 5.5缓冲液中的累积释放率分别是在pH 7.4缓冲液中的2.49倍和2.47倍。Spion-MISO-SpHls的平均粒径为950 nm。PH 7.4缓冲液中Zeta电位为-58.9 mV，pH 5.5缓冲液中Zeta电位为36.3 mV。扫描电子显微镜图像显示Spion-MISO-SpHL具有相似的球形形貌。SPION被包裹在脂质体的中心，在透射电子显微镜图中分散良好。磁化曲线表明Spion-MISO-SpHls保持了超顺磁性。比较Spion-MISO-SpHls和MISO+Spion+空白脂质体对A549细胞缺氧和对照组的影响。相同浓度组(P<；0.0001)和不同时间组(P<；0.0001)的MISO和Spion浓度有显著差异。结论：Spion-MISO-SpHls具有pH依赖的释放能力和超顺磁性，为磁共振下的靶向传递和示踪提供了一个系统。
Background: The use of Misonidazole (MISO), the first and a potential hypoxic tumor cell radiosensitizer, has been limited by peripheral neurotoxicity, thus discouraging phase III clinical trials.Objective: To develop a targeted drug delivery and tracing System with pH-sensitive liposomes (SpHLs) and Superparamagnetic Iron Oxide Nanoparticles (SPIONs) to counter MISO-related adverse effects and to enable tracing under magnetic resonance.Methods: SPION-MISO-SpHLs were prepared by a reverse evaporation and freeze-thawing method. HPLC and phenanthroline spectrophotometry were established for MISO and Fe determination. The characterization and in vitro pH-sensitivity of SPION-MISO-SpHLs were evaluated.Results: The maximal entrapment efficiencies of MISO and SPIONs in SPION-MISO-SpHLs were 30.2% and 23.7%, respectively. The cumulative release rates of MISO and SPIONs were respectively 2.49 and 2.47 times higher in pH 5.5 than in pH 7.4 buffer. The mean particle size of SPION-MISO-SpHLs was 950 nm. The zeta potential was -58.9 mV in pH 7.4 buffer and 36.3 mV in pH 5.5 buffer. SEM imaging showed that SPION-MISO-SpHLs had similar spherical morphologies. SPIONs were packed in the center of liposomes and were well dispersed in a TEM graph. Magnetization curve showed that SPION-MISO-SpHLs retained superparamagnetic properties. SPION-MISO-SpHLs were compared with MISO+SPION+blank liposome in hypoxia and control groups of A549 cells. MISO and SPION concentrations in culture medium showed significant differences between the same concentration groups (P < 0.0001) and at different times (P < 0.0001).Conclusion: SPION-MISO-SpHLs possess pH-dependent release ability and superparamagnetism, and thus provides a system for targeted delivery and tracing under magnetic resonance.