Polypseudorotaxanes of pegylated α-cyclodextrin/polyamidoamine dendrimer conjugate with cyclodextrins as a sustained release system for DNA

Nonviral gene delivery suffers from a number of limitations including short transgene expression times and low transfection efficiency. In this study, we examined whether polypseudorotaxanes (PPRXs) of polyethylene glycol (PEG, molecular weight: 2,000)-grafted alpha-cyclodextrin (alpha-CyD)/polyamidoamine dendrimer conjugate (PEG-alpha-CDE) with CyDs have the potential for the novel sustained release systems for plasmid DNA (pDNA). The PEG-alpha-CDE/pDNA complex formed PPRXs with alpha-CyD and gamma-CyD solutions, but not with beta-CyD solution. In the PEG-alpha-CDE/CyDs PPRX systems, 20.6 mol of alpha-CyD and 11.8 mol of gamma-CyD were involved in the PPRXs formation with one PEG chain by alpha-CyD and gamma-CyD, respectively, consistent with in the PEG-dendrimer/CyDs systems. PEG-alpha-CDE/pDNA/alpha-CyD PPRX and PEG-alpha-CDE/pDNA/gamma-CyD PPRX formed hexagonal and tetragonal columnar channels in the crystalline phase, respectively. In addition, the CyDs PPRX provided the sustained release of pDNA from PEG-alpha-CDE complex with pDNA at least 72 h in vitro. The release of pDNA from CyDs PPRX retarded as the volume of dissolution medium decreased. Furthermore, the PEG-alpha-CDE/gamma-CyD PPRX system showed sustained transfection efficiency after intramuscular injection to mice at least for 14 days. These results suggest that the PEG-alpha-CDE/CyD PPRX systems are useful for novel sustained DNA release systems. (C) 2012 Elsevier Ltd. All rights reserved.