alpha-cyclodextrin has been researched along with Amyloid-Neuropathies--Familial* in 2 studies
2 other study(ies) available for alpha-cyclodextrin and Amyloid-Neuropathies--Familial
| Article | Year |
|---|---|
Potential use of lactosylated dendrimer (G3)/α-cyclodextrin conjugates as hepatocyte-specific siRNA carriers for the treatment of familial amyloidotic polyneuropathy.
To reveal the potential use of lactosylated-dendrimer (G3) conjugates with α-cyclodextrin (Lac-α-CDE (G3)) as novel hepatocyte-specific siRNA carriers in order to treat transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP), we evaluated the RNAi effect of siRNA complexes with Lac-α-CDE (G3) both in vitro and in vivo. Herein, we targeted TTR gene expression because TTR-related FAP was often caused by amyloidogenic TTR (ATTR), which mainly expresses in hepatocytes. Lac-α-CDE (G3, average degree of substitution of lactose (DSL) 1.2)/siRNA complex had a potent RNAi effect against TTR gene expression through adequate physicochemical properties, asialoglycoprotein receptor (ASGP-R)-mediated cellular uptake, efficient endosomal escape and the delivery of the siRNA complex to cytoplasm, but not nucleus, with negligible cytotoxicity. Lac-α-CDE (G3, DSL 1.2)/siRNA complex had the potential to induce the in vivo RNAi effect after intravenous administration in the liver of mice. The blood chemistry values in the α-CDE (G3) and Lac-α-CDE (G3, DSL 1.2) systems were almost equivalent to those in the control system (5% mannitol solution). Taken together, these results suggest that Lac-α-CDE (G3, DSL 1.2) has the potential for a novel hepatocyte-selective siRNA carrier in vitro and in vivo, and has a possibility as a therapeutic tool for FAP to the liver transplantation. Topics: alpha-Cyclodextrins; Amyloid Neuropathies, Familial; Animals; Blotting, Western; Dendrimers; Flow Cytometry; Genetic Vectors; Hep G2 Cells; Hepatocytes; Humans; Lactose; Male; Mice; Microscopy, Fluorescence; Prealbumin; Real-Time Polymerase Chain Reaction; RNA, Small Interfering | 2012 |
Systemic delivery of transthyretin siRNA mediated by lactosylated dendrimer/α-cyclodextrin conjugates into hepatocyte for familial amyloidotic polyneuropathy therapy.
RNA interference (RNAi) is a sequence-specific gene-silencing mechanism triggered by double-stranded RNA and powerful tools for a gene function study and RNAi therapy. Although siRNAs offer several advantages as potential new drugs to treat various diseases, the efficient delivery system of siRNAs in vivo remains a crucial challenge for achieving the desired RNAi effect in clinical development. In particular, when considering the siRNA therapeutics for familial amyloidotic polyneuropathy (FAP) caused by the deposition of variant transthyretin (TTR) in various organs, hepatocyte-selective siRNA delivery is desired because TTR is predominantly synthesized by hepatocytes. In this study, to reveal the potential use of lactosylated dendrimer (G3)/α-cyclodextrin conjugate (Lac-α-CDE (G3)) as novel hepatocyte-selective siRNA carriers in order to treat FAP, we evaluated the RNAi effect of siRNA complex with Lac-α-CDE (G3) both in vitro and in vivo. Topics: alpha-Cyclodextrins; Amyloid Neuropathies, Familial; Animals; Dendrimers; Hepatocytes; Humans; Prealbumin; RNA Interference; RNA, Small Interfering | 2012 |