Preparation and evaluation of polyamidoamine dendrimer conjugate with glucuronylglucosyl-β-cyclodextrin (G3) as a novel carrier for siRNA

被引：14
作者：
Abdelwahab, Ahmed Fouad [1 ,2 ]
Ohyama, Ayumu [1 ,3 ]
Higashi, Taishi [1 ]
Motoyama, Keiichi [1 ]
Khaled, Khaled Ali [2 ]
Sarhan, Hatem Abdelmonsef [2 ]
Hussein, Amal Kamal [2 ]
Arima, Hidetoshi [1 ,3 ]
机构：
[1] Kumamoto Univ, Grad Sch Pharmaceut Sci, Kumamoto 8620973, Japan
[2] Menia Univ, Fac Pharm, Dept Pharmaceut, Al Minya, Egypt
[3] Kumamoto Univ, Program Leading Grad Sch, HIGO Hlth Life Sci Interdisciplinary & Glocal Ori, Kumamoto 8620973, Japan
来源：
JOURNAL OF DRUG TARGETING | 2014年 / 22卷 / 10期
关键词：
Conjugate; glucuronylglucosyl-beta-cyclodextrin; PAMAM dendrimer; siRNA delivery; GENE-TRANSFER; PAMAM DENDRIMERS; RNA INTERFERENCE; IN-VITRO; DELIVERY; EXPRESSION; PROSPECTS; POLYMERS;
D O I：
10.3109/1061186X.2014.950663
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
In this study, we newly synthesized the polyamidoamine STARBURST dendrimer (dendrimer, generation 3: G3) conjugates with 6-O-alpha-(4-O-alpha-D-glucuronyl)-D-glucosyl-beta-cyclodextrin [GUG-beta-CDE (G3)] having the various degrees of substitution (DS) of GUG-beta-cyclodextrin of 1.6, 3.0, 3.7, 5.0 and 8.6, and evaluated them as a siRNA transfer carrier. GUG-beta-CDEs (G3) formed the positively charged and nano-order complexes with siRNA. Of the siRNA complexes with five GUG-beta-CDEs (G3), the complex with GUG-beta-CDE (G3, DS 3.7) showed the highest RNAi effect and cellular uptake with negligible cytotoxicity in KB cells at a charge ratio of 20. In addition, the RNAi effect and cellular uptake of the complex with GUG-beta-CDE (G3, DS 3.7) were higher than those of alpha-CDE (G3, DS 2.4) and comparable to those of Lipofectamine(TM) 2000. Furthermore, the complex with GUG-beta-CDE (G3, DS 3.7) possessed the endosomal escaping ability, the releasing property of siRNA in the cytoplasm and serum resistance. These results suggest that GUG-beta-CDE (G3, DS 3.7) has the potential as a novel siRNA carrier.
引用
收藏
页码：927 / 934
页数：8
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