Effect of cholesteryl side chain and complexing with cholic acid on gene transfection by cationic poly(ethylene glycol) derivatives

A new class of poly(ethylene glycol) derivative, Chol-PEG-A, having both cholesteryl- and amino-pendant groups (2.89 and 5.39 groups per polymer molecule, respectively) was synthesized. This amphiphilic PEG derivative forms a cationic polymer assembly in water. Chol-PEG-A expressed high transfection efficiency in the serum-free medium at relatively low amine/phosphate (N/P) ratios (1.3-1.5), whereas PEG-A, having only amino pendants without the cholesteryl side chain could transfect the cells only at a very high N/P ratio (83). The efficiency remarkably decreased by addition of fetal bovine serum (FBS) to the medium. Mixing of cholic acid to Chol-PEG-A gave a neutralized polyion complex, and the interaction with serum proteins was evidently suppressed. This Chol-PEG-A-cholic acid system showed higher gene expression even in the FBS-containing medium and as high a transfection efficiency as a Superfect. (C) 2001 Elsevier Science B.V. All rights reserved.