Improved cell viability of linear polyethylenimine through γ-cyclodextrin inclusion for effective gene delivery

A polypseudorotaxone consisting of a linear polyethylenimine with M-n of 22000 (LPEl22k) and gamma-cyclodextrins (gamma-CDs; LPEl22k/gamma-CD) has been examined as a gene carrier. The polyplex formation with luciferase-encoding plasmid DNA (pDNA), introcellular trafficking of polyplex, cytotoxicity, and transfection efficiency were evaluated by various characteristic methods. LPEl22k/gamma-CD formed a pDNA polyplex at higher NIP ratios than LPEl22k; this suggests that the gamma-CD threading sterically interfered with the polyplex formation. In addition, the zeta potentials of the polyplex significantly decreased due to the reduction in charge density of LPEI22k caused by gamma-CD, threading. The cellular uptake of pDNA in the LPEl22k/gamma-CD polyplex was enhanced by free gamma-CDs released from the polyplex that might accelerate the cellular uptake through enhanced membrane affinity. LPEl22k/gamma-CD significantly increased cell viability even at high N/P ratios, and the polyplex showed high tronsfection efficacy. The low cytotoxicity and high gene expression of LPEl22k/gamma-CD are advantageous to polyplex administration in vivo.