Bernkop-Schnürch lab - Oligomers, polymers, and nanoparticles for improved cellular uptake
An important factor for successful drug delivery is the internalisation of the carrier systems into the target cells. Due to the anionic nature of the cell membrane and membrane proteins with multiple thiol functionalities on the extracellular site, the introduction of cationic or thiolated moieties on drug carriers leads to stronger cell membrane association and consequently to improved cellular uptake. We have already synthesized several oligo- and polymeric systems, as well as nanoparticles, with numerous cationic and/or thiol units and tested them on different cell lines. Our experiments show that these modified carrier systems can be internalized by the cells to a greater extent than the unmodified analogues. Furthermore, the efflux activity of cell membrane glycoproteins counteracts the increased accumulation of drugs in the cells, decreases their concentration at the target site and leads to reduced therapeutic outcomes and potential drug resistance. Thiolated oligomers showed a high potential to inhibit such efflux and could thus improve the bioavailability of various therapeutics.