RRC ID 43650
Author Motoyama K, Hayashida K, Higashi T, Arima H.
Title Polypseudorotaxanes of pegylated α-cyclodextrin/polyamidoamine dendrimer conjugate with cyclodextrins as a sustained release system for DNA.
Journal Bioorg Med Chem
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.
Volume 20(4)
Pages 1425-33
Published 2012-2-15
DOI 10.1016/j.bmc.2011.12.060
PII S0968-0896(12)00002-8
PMID 22277591
MeSH Animals Cell Line, Tumor Crystallography, X-Ray DNA / chemistry* Delayed-Action Preparations / administration & dosage Delayed-Action Preparations / chemistry* Delayed-Action Preparations / pharmacology Dendrimers / chemistry* Electrophoresis, Gel, Two-Dimensional Injections, Intramuscular Male Mice Mice, Inbred BALB C Molecular Structure Particle Size Polyamines / chemistry* Polyamines / pharmacology Polyethylene Glycols / chemistry Rotaxanes / chemical synthesis Rotaxanes / chemistry* X-Ray Diffraction alpha-Cyclodextrins / chemistry* alpha-Cyclodextrins / pharmacology
IF 3.073
Times Cited 29
WOS Category CHEMISTRY, MEDICINAL CHEMISTRY, ORGANIC BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells