Motoyama Keiichi, Hayashida Kayoko, Arima Hidetoshi
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, Japan.
Chem Pharm Bull (Tokyo). 2011;59(4):476-9. doi: 10.1248/cpb.59.476.
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.
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。