Reference - Detail
| 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 |
| Altmetric score |
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HepG2 KB(RCB1601) |