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聚乙二醇化聚酰胺胺树枝状大分子与环糊精的聚准轮烷作为DNA新型缓释系统的潜在用途。

Potential use of polypseudorotaxanes of pegylated polyamidoamine dendrimer with cyclodextrins as novel sustained release systems for DNA.

作者信息

Motoyama Keiichi, Hayashida Kayoko, Arima Hidetoshi

机构信息

Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, Japan.

出版信息

Chem Pharm Bull (Tokyo). 2011;59(4):476-9. doi: 10.1248/cpb.59.476.

Abstract

In this study, we demonstrated the potential use of polypseudorotaxanes (PPRXs) of polyethylene glycol (PEG, molecular weight: 2000)-grafted polyamidoamine dendrimer (PEG-dendrimer) with cyclodextrins (CyDs) as novel sustained release systems for plasmid DNA (pDNA). PEG-dendrimer/pDNA complex formed PPRXs with α-CyD and γ-CyD solutions, but not with β-CyD solution. In the PEG-dendrimer/CyDs PPRXs systems, 17.9 mol of α-CyD and 8.8 mol of γ-CyD were involved in the PPRXs formation with one PEG chain by α-CyD and γ-CyD, respectively. In addition, the CyDs PPRX formation provided the sustained release of pDNA from PEG-dendrimer complex with pDNA at least 72 h in vitro. In addition, the release of pDNA from CyDs PPRX retarded as the dissolution medium volume decreased. These results suggest that the PEG-dendrimer/CyD PPRX systems can work as a sustained DNA release system, and the PPRX formation with CyDs may be useful as a sustained drug delivery technique for other pegylated polymers.

摘要

在本研究中,我们证明了聚乙二醇(PEG,分子量:2000)接枝的聚酰胺胺树枝状大分子(PEG-树枝状大分子)与环糊精(CyDs)形成的聚准轮烷(PPRXs)作为质粒DNA(pDNA)新型缓释系统的潜在用途。PEG-树枝状大分子/pDNA复合物与α-CyD和γ-CyD溶液形成PPRXs,但与β-CyD溶液不形成。在PEG-树枝状大分子/CyDs PPRXs系统中,α-CyD和γ-CyD分别与一条PEG链形成PPRXs时,α-CyD参与的量为17.9摩尔,γ-CyD参与的量为8.8摩尔。此外,CyDs PPRX的形成使pDNA从与pDNA的PEG-树枝状大分子复合物中至少在体外持续释放72小时。另外,随着溶解介质体积的减小,pDNA从CyDs PPRX中的释放受到阻碍。这些结果表明,PEG-树枝状大分子/CyD PPRX系统可作为一种持续DNA释放系统,并且与CyDs形成PPRX可能作为其他聚乙二醇化聚合物的持续药物递送技术。

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