PMID- 25051178
OWN - NLM
STAT- MEDLINE
DCOM- 20150706
LR  - 20141111
IS  - 1029-2330 (Electronic)
IS  - 1026-7158 (Linking)
VI  - 22
IP  - 10
DP  - 2014 Dec
TI  - Potential use of glucuronylglucosyl-beta-cyclodextrin/dendrimer conjugate (G2) as a 
      siRNA carrier for the treatment of familial amyloidotic polyneuropathy.
PG  - 883-90
LID - 10.3109/1061186X.2014.939984 [doi]
AB  - We previously reported that 6-O-alpha-(4-O-alpha-D-glucuronyl)-D-glucosyl-beta-cyclodextrin 
      (GUG-beta-CyD) conjugate with polyamidoamine dendrimer (dendrimer, generation 2; G2) 
      (GUG-beta-CDE (G2)) is useful as a gene transfer carrier. In the present study, to 
      investigate the potentials of GUG-beta-CDE (G2) as a siRNA carrier, we evaluated the 
      RNAi effect of its complex with siRNA against transthyretin (TTR) mRNA (siTTR) 
      for the treatment of familial amyloidotic polyneuropathy (FAP). Among the various 
      GUG-beta-CDEs (G2) having the different degrees of substitution of GUG-beta-CyD (degree 
      of substation (DS) 1.8, 2.5, 3.0 and 5.0), GUG-beta-CDE (G2, DS 1.8) showed the 
      highest siTTR transfer activity. GUG-beta-CDE (G2, DS 1.8)/siTTR complex showed no 
      cytotoxicity in HepG2 cells. After intravenous administration of GUG-beta-CDE (G2, 
      DS 1.8)/siTTR complex to BALB/c mice, TTR mRNA expression was tended to reduce 
      with negligible change of blood chemistry data. Particle size, zeta-potential and 
      cellular association of the GUG-beta-CDE (G2, DS 1.8) complex were almost the same 
      as those of the other CDEs complexes. Meanwhile, GUG-beta-CDE (G2, DS 1.8)/siTTR 
      complex showed high endosomal escaping ability of siTTR in cytoplasm. These 
      findings suggest the potential of GUG-beta-CDE (G2, DS 1.8) as a siRNA carrier for 
      the FAP treatment.
FAU - Anno, Takayuki
AU  - Anno T
AD  - Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, 
      Kumamoto University , Chuo-ku, Kumamoto , Japan .
FAU - Higashi, Taishi
AU  - Higashi T
FAU - Hayashi, Yuya
AU  - Hayashi Y
FAU - Motoyama, Keiichi
AU  - Motoyama K
FAU - Jono, Hirofumi
AU  - Jono H
FAU - Ando, Yukio
AU  - Ando Y
FAU - Arima, Hidetoshi
AU  - Arima H
LA  - eng
PT  - Journal Article
DEP - 20140722
PL  - England
TA  - J Drug Target
JT  - Journal of drug targeting
JID - 9312476
RN  - 0 (Dendrimers)
RN  - 0 (Oligosaccharides)
RN  - 0 (Poly(amidoamine))
RN  - 0 (Polyamines)
RN  - 0 (Prealbumin)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (cyclomaltoheptaosyl-(6-1)-glucopyranosyl-(4-1)-glucopyranosiduronic acid)
SB  - IM
MH  - Administration, Intravenous
MH  - Amyloid Neuropathies, Familial/genetics/*therapy
MH  - Animals
MH  - Dendrimers/*chemistry
MH  - Endosomes/metabolism
MH  - Gene Transfer Techniques
MH  - Hep G2 Cells
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Oligosaccharides/*chemistry
MH  - Particle Size
MH  - Polyamines/*chemistry
MH  - Prealbumin/genetics
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering/*administration & dosage
OTO - NOTNLM
OT  - Conjugate
OT  - PAMAM dendrimer
OT  - familial amyloidotic polyneuropathy
OT  - glucuronylglucosyl-beta-cyclodextrin
OT  - siRNA
OT  - transthyretin
EDAT- 2014/07/23 06:00
MHDA- 2015/07/07 06:00
CRDT- 2014/07/23 06:00
PHST- 2014/07/23 06:00 [entrez]
PHST- 2014/07/23 06:00 [pubmed]
PHST- 2015/07/07 06:00 [medline]
AID - 10.3109/1061186X.2014.939984 [doi]
PST - ppublish
SO  - J Drug Target. 2014 Dec;22(10):883-90. doi: 10.3109/1061186X.2014.939984. Epub 
      2014 Jul 22.