Preclinical Development – Biomolecular
2019 PharmSci 360
The Blood-Brain Barrier (BBB) is a major obstacle in getting macromolecules across to the brain for treating neurological disorders. Hydroxyethyl-starch(HES)-polyethyleneimine conjugates recently showed promising results in delivering genes in vitro. In this study, we produced biotinylated Hydroxyethyl-starch(HES)-polyethyleneimine conjugates with different molecular weights that can easily be linked to transferrin receptor antibody-Streptavidin (8D3-SA) conjugates for targeted delivery of Oligonucleotides to the brain. The optimal polymer conjugate was selected based on cytotoxicity assay, erythrocyte aggregation assay, oligonucleotide condensation assay particle size and zeta potential analysis. The uptake of 8D3SA alone was assessed through saturable uptake kinetics as well as flow cytometry-based analysis. The optimal polymer conjugate had a particle size of ~100 nm and the targeted polyplexes showed a significantly higher uptake while untargeted polyplexes had minimal uptake in Brain Endothelium. Our results indicate this to be a promising delivery system that could have widespread applications in targeted delivery of Oligonucleotides to the brain endothelium.