title: Polypseudorotaxanes of pegylated α-cyclodextrin/polyamidoamine dendrimer conjugate with cyclodextrins as a sustained release system for DNA.
abstract: 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 α-cyclodextrin (α-CyD)/polyamidoamine dendrimer conjugate (PEG-α-CDE) with CyDs have the potential for the novel sustained release systems for plasmid DNA (pDNA). The PEG-α-CDE/pDNA complex formed PPRXs with α-CyD and γ-CyD solutions, but not with β-CyD solution. In the PEG-α-CDE/CyDs PPRX systems, 20.6mol of α-CyD and 11.8mol of γ-CyD were involved in the PPRXs formation with one PEG chain by α-CyD and γ-CyD, respectively, consistent with in the PEG-dendrimer/CyDs systems. PEG-α-CDE/pDNA/α-CyD PPRX and PEG-α-CDE/pDNA/γ-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-α-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-α-CDE/γ-CyD PPRX system showed sustained transfection efficiency after intramuscular injection to mice at least for 14days. These results suggest that the PEG-α-CDE/CyD PPRX systems are useful for novel sustained DNA release systems.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.forename: Kayoko
authors.initials: K
authors.lastname: Hayashida
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D050091:Dendrimers / Q000737:chemistry*; D015180:Electrophoresis, Gel, Two-Dimensional; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D043862:Rotaxanes / Q000138:chemical synthesis / Q000737:chemistry*; D014961:X-Ray Diffraction; D047391:alpha-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D050091:Dendrimers; C531249:Poly(amidoamine); D011073:Polyamines; D043862:Rotaxanes; D047391:alpha-Cyclodextrins; D011092:Polyethylene Glycols; D004247:DNA