Self-assembled polyethylenimine-graft-poly(epsilon-caprolactone) micelles as potential dual carriers of genes and anticancer drugs.

A series of amphiphilic cationic graft polymers (PEC) were synthesized by coupling poly(epsilon-caprolactone) of differing molecular weights (MW) to low MW branched polyethylenimine via an amide group. IR, (1)H-NMR and GPC were employed to characterize the graft copolymers. The self-assembly characteristics of these copolymers in an aqueous solution were studied by fluorescence techniques. The critical micelle concentration (CMC) varied from 0.044 to 0.032g/L when the MW of poly(epsilon-caprolactone) increased from 1,800 to 5,500. The micelles formed electrostatic complexes with a reporter gene (pCMV-Luc) after an anticancer drug, Doxorubicin (DOX), was loaded by dialysis method. Gel retardation studies proved that micelles with or without DOX were able to complex with DNA completely at an equivalent N/P ratio of around 2.0, indicating that drug loading did not interfere in the interaction between the PEI shell and DNA. Particle size slightly decreased at higher N/P ratios of polyplexes, but increased with drug encapsulation. It was also noted that DNA/micelle complexes were significantly less toxic to HepG2 cells than blank PEC micelles, and improved gene transfection efficiency (about 3 orders of magnitude greater than PEI 25K alone at most) whether DOX was present in the system or not. These results suggest that this group of cationic graft polymers may be a potential candidate for the development of a drug delivery system that can examine the synergistic effects of combined drug and gene therapy.