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Bioorganic and Medicinal Chemistry2012.VOL20-4.pdf625KbAdobe PDFView/Open
Title :Polypseudorotaxanes of Pegylated α-Cyclodextrin/Polyamidoamine Dendrimer Conjugate with Cyclodextrins as a Sustained Release System for DNA
Authors :Motoyama, Keiichi
Hayashida, Kayoko
Higashi, Taishi
Arima, Hidetoshi
Issue Date :15-Feb-2012
Citation jtitle :Bioorganic and Medicinal Chemistry
vol. :20
no. :4
start page :1425
end page :1433
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, 20.6 mol of α-CyD and 11.8 mol 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 14 days. These results suggest that the PEG-α-CDE/CyD PPRX systems are useful for novel sustained DNA release systems.
URL :http://www.sciencedirect.com/science/article/pii/S0968089612000028
Type Local :雑誌掲載論文
ISSN :09680896
Publisher :Elsevier Limited
Rights :© 2012 Elsevier Limited
URI :http://hdl.handle.net/2298/26022
Appears in Collections:Journal Article (Pharmacy)
Please use this identifier to cite or link to this item: http://hdl.handle.net/2298/26022