Carbone C, Campisi A, Manno D, Serra A, Spatuzza M, Musumeci T, Bonfanti R, Puglisi G
Laboratory of Drug Delivery Technology, Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy; Li-Sa Laboratory, Department of Experimental Medicine, Section of Medical Physiopathology, Endocrinology and Nutrition, University La Sapienza of Rome, via S. Sofia 78, Catania, Italy.
Section of Biochemistry, Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
Colloids Surf B Biointerfaces. 2014 Sep 1;121:1-10. doi: 10.1016/j.colsurfb.2014.05.024. Epub 2014 May 27.
Exploiting the experimental factorial design and the potentiality of Turbiscan AG Station, we developed and characterized unmodified and DDAB-coated NLC prepared by a low energy organic solvent free phase inversion temperature technique. A 22 full factorial experimental design was developed in order to study the effects of two independent variables (DDAB and ferulic acid) and their interaction on mean particle size and zeta potential values. The factorial planning was validated by ANOVA analysis; the correspondence between the predicted values of size and zeta and those measured experimentally confirmed the validity of the design and the equation applied for its resolution. The DDAB-coated NLC were significantly affected in their physico-chemical properties by the presence of DDAB, as showed by the results of the experimental design. The coated NLC showed higher physical stability with no particles aggregation compared to the unmodified NLC, as demonstrated by Turbiscan(®) AGS measurements. X-ray diffraction, Raman spectroscopy and Cryo-TEM images allowed us to assert that DDAB plays a critical role in increasing the lipids structural order with a consequent enhancement of the NLC physical stability. Furthermore, the results of the in vitro biological studies allow the revisiting of the role of DDAB to the benefit of glioblastoma treatment, due to its efficacy in increasing the NLC uptake and reducing the viability of human glioblastoma cancer cells (U87MG).
利用实验因子设计和Turbiscan AG Station的潜力,我们开发并表征了通过低能量无有机溶剂相转变温度技术制备的未修饰和DDAB包覆的纳米脂质载体(NLC)。为了研究两个自变量(DDAB和阿魏酸)及其相互作用对平均粒径和zeta电位值的影响,我们开展了一项2²全因子实验设计。通过方差分析(ANOVA)验证了因子规划;粒径和zeta电位的预测值与实验测量值之间的对应关系证实了该设计以及用于其解析的方程的有效性。如实验设计结果所示,DDAB的存在显著影响了DDAB包覆的NLC的物理化学性质。Turbiscan® AGS测量结果表明,与未修饰的NLC相比,包覆的NLC表现出更高的物理稳定性,没有颗粒聚集现象。X射线衍射、拉曼光谱和冷冻透射电子显微镜(Cryo-TEM)图像使我们能够断言,DDAB在增加脂质结构有序性方面起着关键作用,从而增强了NLC的物理稳定性。此外,体外生物学研究结果使我们能够重新审视DDAB在胶质母细胞瘤治疗中的作用,因为它在增加NLC摄取和降低人胶质母细胞瘤癌细胞(U87MG)活力方面具有功效。