| RRC ID |
34559
|
| Author |
Arima H, Yamashita S, Mori Y, Hayashi Y, Motoyama K, Hattori K, Takeuchi T, Jono H, Ando Y, Hirayama F, Uekama K.
|
| Title |
In vitro and in vivo gene delivery mediated by Lactosylated dendrimer/alpha-cyclodextrin conjugates (G2) into hepatocytes.
|
| Journal |
J Control Release
|
| Abstract |
The purpose of this study is to evaluate in vitro and in vivo gene delivery efficiency of polyamidoamine (PAMAM) starburst dendrimer (generation 2, G2) conjugates with alpha-cyclodextrin (alpha-CDE (G2)) bearing lactose (Lac-alpha-CDE) with various degrees of substitution of the lactose moiety (DSL) as a novel hepatocyte-selective carrier in hepatocytes. Lac-alpha-CDE (DSL 2.6) was found to have much higher gene transfer activity than dendrimer, alpha-CDE, Lac-alpha-CDE (DSL 1.2, 4.6, 6.2 and 10.2) and lactosylated dendrimer (Lac-dendrimer, DSL 2.4) in HepG2 cells, which are dependent on the expression of cell-surface asialoglycoprotein receptor (ASGP-R), reflecting the cellular association of the plasmid DNA (pDNA) complexes. The physicochemical properties of pDNA complex with Lac-alpha-CDE (DSL 2.6) were almost comparable to that with alpha-CDE. Lac-alpha-CDE (DSL 2.6) provided negligible cytotoxicity up to a charge ratio of 150 in HepG2 cells. Lac-alpha-CDE (DSL 2.6) provided gene transfer activity higher than jetPEI-Hepatocyte to hepatocytes with much less changes of blood chemistry values 12h after intravenous administration in mice. These results suggest the potential use of Lac-alpha-CDE (DSL 2.6) as a non-viral vector for gene delivery toward hepatocytes.
|
| Volume |
146(1)
|
| Pages |
106-17
|
| Published |
2010-8-17
|
| DOI |
10.1016/j.jconrel.2010.05.030
|
| PII |
S0168-3659(10)00398-6
|
| PMID |
20678990
|
| MeSH |
Animals
Cell Culture Techniques
DNA / administration & dosage
DNA / genetics*
Dendrimers / chemistry*
Drug Carriers / chemistry*
Flow Cytometry
Gene Transfer Techniques*
Hepatocytes / metabolism*
Humans
KB Cells
Lactose / chemistry*
Liver / metabolism
Male
Mice
Mice, Inbred BALB C
Microscopy, Confocal
Organ Specificity
Plasmids
Polyethyleneimine / chemistry
Surface Plasmon Resonance
alpha-Cyclodextrins / chemistry*
|
| Times Cited |
3
|
|
WOS Category
|
MEDICINE, RESEARCH & EXPERIMENTAL
PHARMACOLOGY & PHARMACY
|
| Resource |
| Human and Animal Cells |
HepG2
KB(RCB1601) |
