Improvements in rational design strategies of inulin derivative polycation for sirna delivery.

IMPROVEMENTS IN RATIONAL DESIGN STRATEGIES OF INULIN DERIVATIVE POLYCATION FOR SIRNA DELIVERY. Biomacromolecules. 2016 May 29; Authors: Sardo C, Craparo EF, Porsio B, Giammona G, Cavallaro G Abstract The advances of short interfering RNA (siRNA) mediated therapy provide a powerful option for the treatment of many diseases, including cancer, by silencing the expression of targeted genes involved in the progression of the pathology. On this regard, a new pH-responsive polycation derived from inulin, Inulin-g-imidazole-g-diethylenetriamine (INU-IMI-DETA), was designed and employed to produce INU-IMI-DETA/siRNA "Inulin COmplex Nanoaggregates" (ICONs). The experimental results showed that INU-IMI-DETA exhibited strong cationic characteristics and high solubility in the pH range 3-5 and self aggregation triggered by pH increase and physiological salt concentration. INU-IMI-DETA showed as well an high buffering capacity in the endosomal pH range of 7.4-5.1. In the concentration range between 25 and 1000 µg/ml INU-IMI-DETA had no cytotoxic effect on breast cancer cells (MCF-7) and no lytic effect on human red blood cells. ICONs were prepared by two-step procedure involving complexation and precipitation into DPBS buffer (pH 7.4) to produce siRNA loaded nanoaggregates with minimized surface charge and suitable size for parenteral administration. Bafilomycin A1 inhibited transfection on MCF-7 cells, indicating that the protonation of the imid...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research