School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, PR China.
School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, PR China.
Int J Biol Macromol. 2019 Mar 1;124:667-680. doi: 10.1016/j.ijbiomac.2018.11.258. Epub 2018 Nov 28.
This study explored the feasibility of using smart nanocaged carrier technology for the delivering of multifunctional mPEG-chitosan stabilized silybin nanocrystals and to enhancing the long-term stability, dissolution velocity and bioavailability of the water insoluble drugs. The methoxypoly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL), as nanocaged carrier, was modified with propargyl and azide group and confirmed by FTIR. The methoxypolythylene glycol-grafted chitosan (PEG-CS), as multifunctional stabilizer, were applied for the silybin nanocrystals formulation. Two silybin nanocrystals formulations (PEG-CS nanocrystals and nanocaged nanocrystals) were prepared using anti-solvent precipitation method and optimized by central composite design-response surface model. The transmission electron microscopy, scanning electron microscopy and atomic force microscope revealed small and uniformed morphology. The crystalline state of the nanocrystals was confirmed by X-ray powder diffraction and differential scanning calorimetry. The drug structure was confirmed by Fourier transform infrared spectroscopy. During the long term stability study, the nanocaged nanocrystals were presented remarkable stability. Compared with the silybin solution, the nanocaged nanocrystals and the PEG-CS nanocrystals drug delivery system also exhibited 5.54 and 2.58 fold increasing in the AUC, respectively. Thus, the nanocaged nanocrystals technology with excellent stability, improved dissolution velocity and relative bioavailability was recommended as an efficient and feasible approach for water insoluble drugs delivery.
本研究探索了使用智能纳米笼载体技术递送多功能 mPEG-壳聚糖稳定的水飞蓟宾纳米晶体的可行性，并提高了水不溶性药物的长期稳定性、溶解速度和生物利用度。作为纳米笼载体的甲氧基聚（乙二醇）-b-聚（ε-己内酯）（mPEG-b-PCL）经傅里叶变换红外光谱（FTIR）证实进行了炔丙基和叠氮基团的修饰。作为多功能稳定剂的甲氧基聚乙二醇接枝壳聚糖（PEG-CS）被应用于水飞蓟宾纳米晶体的配方。采用反溶剂沉淀法制备了两种水飞蓟宾纳米晶体制剂（PEG-CS 纳米晶体和纳米笼纳米晶体），并通过中心复合设计-响应面模型进行了优化。透射电子显微镜、扫描电子显微镜和原子力显微镜显示出小而均匀的形态。纳米晶体的结晶状态通过 X 射线粉末衍射和差示扫描量热法得到确认。傅里叶变换红外光谱证实了药物结构。在长期稳定性研究中，纳米笼纳米晶体表现出显著的稳定性。与水飞蓟宾溶液相比，纳米笼纳米晶体和 PEG-CS 纳米晶体药物递送系统的 AUC 分别增加了 5.54 倍和 2.58 倍。因此，具有优异稳定性、改善溶解速度和相对生物利用度的纳米笼纳米晶体技术被推荐为一种有效的、可行的水不溶性药物递送方法。
