a College of Pharmacy , Xinxiang Medical University , Xinxiang , P.R. China.
b Department of Pharmacy , The First Affiliated Hospital of Xinxiang Medical University , Weihui , China.
J Biomater Sci Polym Ed. 2018 Oct;29(15):1799-1811. doi: 10.1080/09205063.2018.1498720. Epub 2018 Sep 29.
In this study, a novel chitosan (CS)-modified nanoparticles (NPs) were developed to orally deliver tolbutamide (TOL). Methoxy poly(ethylene glycol)- b-poly(ε-caprolactone) carboxylates (mPEG-b-PCL) was synthesized via an esterification reaction. CS-modified mPEG-b-PCL-COOH NPs (CS@NPs) were fabricated by injecting mPEG-b-PCL-COOH NPs suspension (1.0 mg/mL) into CS solution (1.0 mg/mL, pH 5.0). Fourier transform infrared spectroscopy (FTIR) spectra were used to confirm the obtaining of mPEG-b-PCL-COOH. Transmission electron microscope (TEM) was carried out to observe morphology of all NPs. Nano ZS90 Malvern ParticleSizer were used to monitor the size distribution of obtained NPs. Thermogravimetry analysis (TGA) was performed to investigate the thermostability of CS@NPs. In vitro TOL release profiles were carried out in pH 1.2 and 7.4 buffers. FTIR spectra confirmed the obtaining of mPEG-b-PCL-COOH. TGA curves indicated that the protection of CS shells improved the thermostability of mPEG-b-PCL-COOH NPs. Cell tests indicated the CS@NPs had no obvious cytotoxicity, and they were easily taken up by 293T cells. In vitro release profiles showed that 91.0 ± 1.9% of encapsulated TOL were released from TOL-CS@NPs in pH 7.4 buffer. Therefore, the positive potential of CS@NPs could increase their combining capacity with intestinal mucosal cells. Finally, these NPs would improve the bioavailability of hydrophobic drugs.
在这项研究中，开发了一种新型壳聚糖（CS）修饰的纳米粒子（NPs），用于口服传递甲苯磺丁脲（TOL）。通过酯化反应合成了甲氧基聚（乙二醇）-b-聚（ε-己内酯）羧酸酯（mPEG-b-PCL-COOH）。通过将 mPEG-b-PCL-COOH NPs 悬浮液（1.0mg/mL）注入 CS 溶液（1.0mg/mL，pH5.0）来制备 CS 修饰的 mPEG-b-PCL-COOH NPs（CS@NPs）。傅里叶变换红外光谱（FTIR）谱用于确认 mPEG-b-PCL-COOH 的获得。通过透射电子显微镜（TEM）观察所有 NPs 的形态。纳米 ZS90 Malvern 颗粒粒度仪用于监测获得的 NPs 的粒径分布。热重分析（TGA）用于研究 CS@NPs 的热稳定性。在 pH1.2 和 7.4 缓冲液中进行体外 TOL 释放曲线。FTIR 谱证实了 mPEG-b-PCL-COOH 的获得。TGA 曲线表明 CS 壳的保护提高了 mPEG-b-PCL-COOH NPs 的热稳定性。细胞试验表明 CS@NPs 无明显细胞毒性，并且容易被 293T 细胞摄取。体外释放曲线表明，在 pH7.4 缓冲液中，TOL-CS@NPs 中包裹的 TOL 有 91.0±1.9%释放出来。因此，CS@NPs 的正电势可以增加它们与肠黏膜细胞的结合能力。最后，这些 NPs 将提高疏水性药物的生物利用度。
