Synthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for siRNA delivery in human glioblastoma cells: in-vitro analysis.

Synthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for siRNA delivery in human glioblastoma cells: in-vitro analysis.
Eur J Pharm Sci. 2015 Feb 19;
Authors: Gooding M, Malhotra M, McCarthy DJ, Godinho BM, Cryan JF, Darcy R, O'Driscoll CM
Abstract
In man brain cancer is an aggressive, malignant form of tumor, it is highly infiltrative in nature, is associated with cellular heterogeneity and affects cerebral hemispheres of the brain. Current drug therapies are inadequate and an unmet clinical need exists to develop new improved therapeutics. The ability to silence genes associated with disease progression by using short interfering RNA (siRNA) presents the potential to develop safe and effective therapies. In this work, in order to protect the siRNA from degradation, promote cell specific uptake and enhance gene silencing efficiency, a PEGylated cyclodextrin (CD)-based nanoparticle tagged with a CNS-targeting peptide derived from the rabies virus glycoprotein (RVG) was formulated and characterized. The modified cyclodextrin derivatives were synthesized and co-formulated to form nanoparticles containing siRNA which were analyzed for size, surface charge, stability, cellular uptake and gene-knockdown in brain cancer cells. The results identified an optimized co-formulation prototype at a molar ratio of 1:1.5:0.5 (cationic cyclodextrin: PEGylated cyclodextrin: RVG-tagged PEGylated cyclodextrin) wi...

Source: European Journal of Pharmaceutical Sciences - February 19, 2015 Category: Drugs & Pharmacology Authors: Gooding M, Malhotra M, McCarthy DJ, Godinho BM, Cryan JF, Darcy R, O'Driscoll CM Tags: Eur J Pharm Sci Source Type: research