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使用铵基室温离子液体制备包载紫杉醇的碳纳米管聚己内酯微球:作为一种持续给药系统

Production of CNT-taxol-embedded PCL microspheres using an ammonium-based room temperature ionic liquid: as a sustained drug delivery system.

作者信息

Kim Seong Yeol, Hwang Ji-Young, Seo Jae-Won, Shin Ueon Sang

机构信息

Department of Nanobiomedical Science & BK21 PlUS NBM Global Research Center for Regenerative Medicine, Dankook University, Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam 330-714, Republic of Korea.

Department of Biomedical Engineering, Korea University, Jeongeug-dong, Seongbuk-gu, Seoul 136-703, Republic of Korea.

出版信息

J Colloid Interface Sci. 2015 Mar 15;442:147-53. doi: 10.1016/j.jcis.2014.11.044. Epub 2014 Nov 22.

DOI:10.1016/j.jcis.2014.11.044
PMID:25527087
Abstract

We describe a one-pot method for the mass production of polymeric microspheres containing water-soluble carbon-nanotube (w-CNT)-taxol complexes using an ammonium-based room temperature ionic liquid. Polycaprolactone (PCL), trioctylmethylammonium chloride (TOMAC; liquid state from -20 to 240°C), and taxol were used, respectively, as a model polymer, room temperature ionic liquid, and drug. Large quantities of white colored PCL powder without w-CNT-taxol complexes and gray colored PCL powders containing w-CNT-taxol (1:1 or 1:2 wt/wt) complexes were produced by phase separation between the hydrophilic TOMAC and the hydrophobic PCL. Both microsphere types had a uniform, spherical structure of average diameter 3-5μm. The amount of taxol embedded in PCL microspheres was determined by HPLC and (1)H NMR to be 8-12μg per 1.0mg of PCL (loading capacity (LC): 0.8-1.2%; entrapment efficiency (EE): 16-24%). An in vitro HPLC release assay showed sustain release of taxol without an initial burst over 60days at an average rate of 0.003-0.0073mg per day. The viability patterns of human breast cancer cells (MCF-7) for PCTx-1 and -2 showed dose-dependent inhibitory effects. In the presence of PCTx-1 and -2, the MCF-7 cells showed high viability in the concentration level of, respectably, <70 and <5μg/mL.

摘要

我们描述了一种使用铵基室温离子液体大规模生产含有水溶性碳纳米管(w-CNT)-紫杉醇复合物的聚合物微球的一锅法。分别使用聚己内酯(PCL)、三辛基甲基氯化铵(TOMAC;-20至240°C为液态)和紫杉醇作为模型聚合物、室温离子液体和药物。通过亲水性TOMAC和疏水性PCL之间的相分离,制备出了大量不含w-CNT-紫杉醇复合物的白色PCL粉末以及含有w-CNT-紫杉醇(1:1或1:2重量/重量)复合物的灰色PCL粉末。两种微球类型均具有平均直径为3-5μm的均匀球形结构。通过高效液相色谱法(HPLC)和核磁共振氢谱(¹H NMR)测定,PCL微球中包封的紫杉醇量为每1.0mg PCL含8-12μg(载药量(LC):0.8-1.2%;包封率(EE):16-24%)。体外HPLC释放试验表明,紫杉醇在60天内持续释放,无初始突释,平均释放速率为每天0.003-0.0073mg。人乳腺癌细胞(MCF-7)对PCTx-1和-2的活力模式显示出剂量依赖性抑制作用。在PCTx-1和-2存在的情况下,MCF-7细胞在浓度分别<70和<5μg/mL时显示出高活力。

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