title: Preparation and evaluation of polyamidoamine dendrimer conjugate with glucuronylglucosyl-β-cyclodextrin (G3) as a novel carrier for siRNA.
abstract: Abstract In this study, we newly synthesized the polyamidoamine STARBURST dendrimer (dendrimer, generation 3: G3) conjugates with 6-O-α-(4-O-α-D-glucuronyl)-D-glucosyl-β-cyclodextrin [GUG-β-CDE (G3)] having the various degrees of substitution (DS) of GUG-β-cyclodextrin of 1.6, 3.0, 3.7, 5.0 and 8.6, and evaluated them as a siRNA transfer carrier. GUG-β-CDEs (G3) formed the positively charged and nano-order complexes with siRNA. Of the siRNA complexes with five GUG-β-CDEs (G3), the complex with GUG-β-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-β-CDE (G3, DS 3.7) were higher than those of α-CDE (G3, DS 2.4) and comparable to those of Lipofectamine™ 2000. Furthermore, the complex with GUG-β-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-β-CDE (G3, DS 3.7) has the potential as a novel siRNA carrier.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University , Kumamoto , Japan .
authors.forename: Ahmed Fouad
authors.initials: AF
authors.lastname: Abdelwahab
authors.forename: Ayumu
authors.initials: A
authors.lastname: Ohyama
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.forename: Khaled Ali
authors.initials: KA
authors.lastname: Khaled
authors.forename: Hatem Abdelmonsef
authors.initials: HA
authors.lastname: Sarhan
authors.forename: Amal Kamal
authors.initials: AK
authors.lastname: Hussein
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D050091:Dendrimers / Q000737:chemistry*; D011992:Endosomes / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D007624:KB Cells; D008055:Lipids / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D050091:Dendrimers; D008055:Lipids; C086724:Lipofectamine; D009844:Oligosaccharides; C104700:PAMAM Starburst; D034741:RNA, Small Interfering; C438085:cyclomaltoheptaosyl-(6-1)-glucopyranosyl-(4-1)-glucopyranosiduronic acid
keywords: Conjugate; PAMAM dendrimer; glucuronylglucosyl-β-cyclodextrin; siRNA delivery