Influence of the Molecular Weight of Bioreducible Oligoethylenimine Conjugates on the Polyplex Transfection Properties
Journal Title: The AAPS Journal - Year 2009, Vol 11, Issue 3
Abstract
The purpose of the present study was to investigate the influence of molecular weights on the chemical, biophysical, and biological properties of bioreducible oligoethylenimine conjugates. The cationic conjugates were synthesized by polyaddition between branched oligoethylenimine 800 Da (OEI) and the disulfide bond containing N,N′-cystamine bisacrylamide (CBA) linker. A correlation between the copolymer molecular weights and the polyplex transfection properties was found. The OEI–CBA copolymers differing in molecular weights (from 8.6 to 37 kDa) showed good plasmid DNA binding ability resulting in compact 90- to 150-nm-sized polyplexes. Colloidal stability of the polyplexes was lost in reductive environment. A low concentration of dithiothreitol of 5 µM was sufficient to render polyplexes unstable in size. Reducing conditions at physiological salt concentration triggered polyplex dissociation. The bioreducible polymers displayed much lower cytotoxicity (IC50 ∼ 100 μg/mL in cell culture) than branched polyethylenimine 25 kDa (BPEI) and linear polyethylenimine 22 kDa (LPEI). Reporter gene transfection experiments were done with CHO-K1 and B16-F10 cells. The largest (37 kDa) copolymer HC-6-8 demonstrated highest transfection levels among all the bioreducible copolymers, which was comparable with LPEI and much more effective than BPEI.
Authors and Affiliations
Haijun Yu, Verena Russ, Ernst Wagner
Homology modeling of opioid receptor-ligand complexes using experimental constraints
Opioid receptors interact with a variety of ligands, including endogenous peptides, opiates, and thousands of synthetic compounds with different structural scaffolds. In the absence of experimental structures of opioid r...
Ligand Binding Assays in the 21st Century Laboratory—A Call for Change
In June 2009, a group of ligand binding assay experts met in Seattle, WA to discuss the need for greater efficiency in bioanalytical laboratories. The central premise was increased utilization of technological innovation...
Delivery of siRNA Therapeutics: Barriers and Carriers
RNA interference is a naturally occurring endogenous regulatory process where short double-stranded RNA causes sequence-specific posttranscriptional gene silencing. Small interference RNA (siRNA) represents a promising t...
Optimization of chlorphenesin emulgel formulation
This study was conducted to develop an emulgel formulation of chlorphenesin (CHL) using 2 types of gelling agents: hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The influence of the type of the gelling agent and...
Hyaluronidase-Sensitive Nanoparticle Templates for Triggered Release of HIV/AIDS Microbicide In Vitro
The online version of this article (doi:10.1208/s12248-013-9546-7) contains supplementary material, which is available to authorized users.