Multifunctional drug carrier based on PEI derivatives loaded with small interfering RNA for therapy of liver cancer

Publication date: Available online 17 April 2019Source: International Journal of PharmaceuticsAuthor(s): Yarong Zhao, Robert J. Lee, Luotong Liu, Shiyan Dong, Jing Zhang, Yu Zhang, Yicheng Yao, Jiahui Lu, Qingfan Meng, Jing Xie, Lesheng TengAbstractGene therapy strategies for liver cancer have broad application prospects but still lack a stable and efficient delivery vehicle. To overcome this obstacle, we designed a multifunctional gene delivery vector, sTPssOLP, which was based on oleylamine (OA)-modified disulfide-containing polyethylenimine (PEI) and incorporated into lipids to prepare a lipid nanoparticle. sTPssOLP consisted of the core of PEI derivative and cationic lipids bound to siRNA. The modified polyethylene glycol (PEG) and transferrin (Tf) were partially embedded in the phospholipid bilayer through the lipid and the other as the outer shell. The aim was to use the redox responsiveness of disulfide to trigger siRNA release in cytoplasm to enhance transfection efficiency. Pegylated lipids and Tf focus on increasing cycle life in the body and increasing accumulation at the tumor site of the carrier. In addition, two vectors were prepared as controls, one based on a PEI derivative containing no disulfide bond (POLP) and the other on the surface of the carrier not linked to Tf (PssOLP). PEI derivatives effectively avoid the toxicity problems caused by the use of PEI alone (25 kDa). Meanwhile, it was confirmed by gel retardation experiments that in the presence of dith...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research