Bai Meng-Yi, Tang Sung-Ling, Chuang Meng-Han, Wang Ting-Ying, Hong Po-da
Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
Biomedical Engineering Program, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan.
Front Pharmacol. 2018 Sep 21;9:1025. doi: 10.3389/fphar.2018.01025. eCollection 2018.
We developed a novel, pH-sensitive drug delivery microparticle based on palmitoyl chitosan (NPCS) to transport the superparamagnetic iron oxide (SPIO) and anticancer drug doxorubicin (DOX). The characteristics of NPCS were characterized through nuclear magnetic resonance. Our results based on testing of volume swelling in multiple pH aqueous solutions revealed that the modified chitosan had a pH-sensitive property. The morphology and size of the DOX-SPIO/NPCS microparticles were investigated using transmission electron microscopy and scanning electron microscopy. The statistical result of microparticles had diameter of 185 ± 87 nm. Surface chemical moieties of DOX-SPIO/NPCS microparticles were confirmed using attenuated total reflection Fourier transform infrared spectroscopy and indicated the existence of mostly hydrophilic groups such as -OH, -C=O, and -C-O-C-. Transmission electron microscopy revealed the dark contrast of SPIO dots encapsulated in the NPCS matrix. Nuclear magnetic resonance T2-weighted magnetic resonance imaging confirmed that the produced DOX-SPIO/NPCS microparticles still exhibited T2 relaxation durations as short as 37.68 ± 8.69 ms (under administration of 2.5 μg/mL), which is comparable to the clinically required dosage. In the drug release profile, the DOX-SPIO/NPCS drug delivery microparticle was accelerated in an acidic environment (pH 6.5) compared with that in a basic environment. Microparticles in a cytotoxicity assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay) revealed that DOX-SPIO/NPCS microparticles had better antitumor ability than did free-form of DOX. Additionally, microparticles loaded with 0.5-5 μg/mL DOX in an acidic environment (pH 6.5) demonstrated higher efficacy against Hep G2 cell growth, possibly because of the swelling effect of NPCS, resulting in volume expansion and easy drug release. Accordingly, these large DOX-SPIO/NPCS microparticles showed potential for application as a pH-sensitive drug delivery system and as chemoembolization particles for hepatic carcinoma therapy.
我们开发了一种基于棕榈酰壳聚糖（NPCS）的新型pH敏感药物递送微粒，用于运输超顺磁性氧化铁（SPIO）和抗癌药物阿霉素（DOX）。通过核磁共振对NPCS的特性进行了表征。我们基于在多种pH值水溶液中体积溶胀测试的结果表明，改性壳聚糖具有pH敏感特性。使用透射电子显微镜和扫描电子显微镜研究了DOX-SPIO/NPCS微粒的形态和尺寸。微粒的统计结果显示直径为185±87nm。使用衰减全反射傅里叶变换红外光谱法确认了DOX-SPIO/NPCS微粒的表面化学基团，并表明存在大多数亲水基团，如-OH、-C=O和-C-O-C-。透射电子显微镜显示封装在NPCS基质中的SPIO点具有暗对比度。核磁共振T2加权磁共振成像证实，所制备的DOX-SPIO/NPCS微粒在给药2.5μg/mL时仍表现出短至37.68±8.69ms的T2弛豫时间，这与临床所需剂量相当。在药物释放曲线中，与碱性环境相比，DOX-SPIO/NPCS药物递送微粒在酸性环境（pH 6.5）中释放加速。细胞毒性试验（3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐试验）中的微粒显示，DOX-SPIO/NPCS微粒比游离形式的DOX具有更好的抗肿瘤能力。此外，在酸性环境（pH 6.5）中负载0.5-5μg/mL DOX的微粒对Hep G2细胞生长显示出更高的疗效，这可能是由于NPCS的溶胀作用，导致体积膨胀和药物易于释放。因此，这些大的DOX-SPIO/NPCS微粒显示出作为pH敏感药物递送系统和肝癌治疗的化疗栓塞颗粒的应用潜力。
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