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基于离子组装纳米粒子的双重响应控制药物传递。

Dual-responsive controlled drug delivery based on ionically assembled nanoparticles.

机构信息

School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, PR China.

出版信息

Langmuir. 2012 Jun 26;28(25):9413-20. doi: 10.1021/la3016436. Epub 2012 Jun 6.

Abstract

Ionically assembled nanoparticles (INPs) have been formed from poly(ionic liquid-co-N-isopropylacrylamide) with deoxycholic acid through electrostatic interaction. The structure and properties of the INPs were investigated by using (1)H NMR, Fourier transform infrared (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS), and so on. Due to pH-responsive deoxycholic acid (pK(a) = 6.2) and thermo responsive N-isopropylacrylamide included in the ionic complex, the INPs exhibit highly pH and thermal dual-responsive properties. The potential practical applications as drug delivery carriers were demonstrated using doxorubicin (DOX) as a model drug. With a lower pH (pH 5.2) and higher temperature (above 37 °C), structural collapse of the INPs occurred as well as release of DOX owing to protonated DA departure from the INPs and a lower LCST (lower critical solution temperature) at the pathological conditions. The result shows that 80% of DOX molecules were released from INPs within 48 h at pH 5.2, 43 °C, but only 30% of the drug was released within 48 h at 37 °C and pH 7.4. Moreover, drug-loaded INPs exhibit an inhibitory effect on cell growth.

摘要

通过静电相互作用,从聚(离子液体-共-N-异丙基丙烯酰胺)与脱氧胆酸形成离子组装纳米颗粒(INPs)。通过使用(1)H NMR、傅里叶变换红外(FTIR)、透射电子显微镜(TEM)、动态光散射(DLS)等方法研究了 INPs 的结构和性能。由于包含在离子复合物中的 pH 响应脱氧胆酸(pK(a)= 6.2)和热响应 N-异丙基丙烯酰胺,INPs 表现出高度的 pH 和热双重响应特性。使用阿霉素(DOX)作为模型药物证明了其作为药物递送载体的潜在实际应用。在较低的 pH(pH 5.2)和较高的温度(高于 37°C)下,由于质子化的 DA 从 INPs 中脱离以及病理条件下较低的 LCST(较低临界溶液温度),INPs 的结构崩溃并释放 DOX。结果表明,在 pH 5.2、43°C 下,80%的 DOX 分子在 48 小时内从 INPs 中释放,但在 37°C 和 pH 7.4 下,48 小时内仅释放 30%的药物。此外,载药 INPs 对细胞生长具有抑制作用。

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