Popat Amirali, Karmakar Surajit, Jambhrunkar Siddharth, Xu Chun, Yu Chengzhong
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia; The School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia; Mucosal Diseases Group, Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia.
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
Colloids Surf B Biointerfaces. 2014 May 1;117:520-7. doi: 10.1016/j.colsurfb.2014.03.005. Epub 2014 Mar 19.
Curcumin (CUR), a naturally derived anti-cancer cocktail is arguably the most widely studied neutraceutical. Despite a lot of promises, it is yet to reach the market as an active anti-cancer formulation. In the present study, we have prepared highly soluble (3 mg/ml) CUR-γ-hydroxypropyl cyclodextrin (CUR-CD) hollow spheres. CUR-CD hollow spheres were prepared by a novel and scalable spray drying method. CUR-CD was then encapsulated into positively charged biodegradable chitosan (CUR-CD-CS) nanoparticles. The CUR-CD-CS nanoparticles were characterised by TEM, SEM, DLS, drug loading and in vitro release. We tested the efficacy of these CUR-CD-CS nanoparticles in SCC25 cell lines using MTT assay and investigated its cellular uptake mechanism. We also studied Oligo DNA loading in CUR-CD-CS nanoparticles and its delivery via confocal imaging and FACS analysis. Our results demonstrated that CUR-CD-CS nanoparticles showed superior in vitro release performance and higher cytotoxicity in SCC25 cell line amongst all tested formulations. The cytotoxicity results were corroborated by cell cycle analysis and apoptosis test, showing nearly 100% apoptotic cell death in the case of CUR-CD-CS nanoparticles. Compared to CS nanoparticles, CS-CD nanoformulation showed higher cellular delivery of Cy3-Oligo DNA which was tested quantitatively using flowcytometry analysis, indicating that CD not only enhanced CUR solubility but also boosted the cellular uptake. Our study shows that rationally designed bio-degradable natural biomaterials have great potential as next generation nano-carriers for hydrophobic drug delivery such as CUR with potential of dual drug-gene delivery.
姜黄素（CUR）是一种天然衍生的抗癌合剂，可以说是研究最为广泛的营养保健品。尽管前景广阔，但它作为一种有效的抗癌制剂尚未进入市场。在本研究中，我们制备了高溶解性（3毫克/毫升）的姜黄素-γ-羟丙基环糊精（CUR-CD）空心球。CUR-CD空心球通过一种新颖且可扩展的喷雾干燥法制备。然后将CUR-CD封装到带正电荷的可生物降解壳聚糖（CUR-CD-CS）纳米颗粒中。通过透射电子显微镜（TEM）、扫描电子显微镜（SEM）、动态光散射（DLS）、载药量和体外释放对CUR-CD-CS纳米颗粒进行了表征。我们使用MTT法测试了这些CUR-CD-CS纳米颗粒在SCC25细胞系中的功效，并研究了其细胞摄取机制。我们还研究了寡聚DNA在CUR-CD-CS纳米颗粒中的负载情况及其通过共聚焦成像和荧光激活细胞分选（FACS）分析的递送情况。我们的结果表明，在所有测试制剂中，CUR-CD-CS纳米颗粒在SCC25细胞系中表现出优异的体外释放性能和更高的细胞毒性。细胞周期分析和凋亡测试证实了细胞毒性结果，显示CUR-CD-CS纳米颗粒情况下细胞凋亡死亡近100%。与壳聚糖纳米颗粒相比，壳聚糖-环糊精纳米制剂对Cy3-寡聚DNA的细胞递送更高，这通过流式细胞术分析进行了定量测试，表明环糊精不仅提高了姜黄素的溶解度，还增强了细胞摄取。我们的研究表明，合理设计的可生物降解天然生物材料作为下一代纳米载体具有巨大潜力，可用于递送疏水性药物如姜黄素，并具有双药-基因递送的潜力。
