Double conjugated nanogels for selective intracellular drug delivery

Abstract

One of the most important drawbacks of nanomedicine is related to the unwanted rapid diffusion of drugs loaded within nanocarriers towards the external biological environment, according to the high clearance of body fluids. Therefore, colloids can carry only a small amount of their initial content in the target district, limiting their pharmacological activity and then the therapy. To overcome this limitation, we synthesized double conjugated nanogels: the first click strategy (1,3 Huisgen cycloaddition) guarantees the traceability of nanogels while the second one (disulfide bond) links drug molecules to polymeric chains. In this study, we proposed the above-mentioned double strategy and we validated the synthesized colloids and the selective release kinetics in microglia cells, dramatically involved in several diseases of the central nervous system. Cleavable linked drugs prove to be a promising tool for the selective administration of pharmacological compounds in microglia cells and potentially in many others counteracting some relevant events.