Abstract:
In this study, biodegradable nanogels were fabricated using supramolecular host-guest type interactions between a βCD-grafted dextran polymer and disulfide-containing bis-adamantane based linkers. These nanogels were designed to exhibit redox-responsive diassembly when exposed to reducing agents such as glutahione and dithiothreitol (DTT). First generation nanogels were fabricated using the βCD-grafted dextran polymer and a disulfide-containing hydrophobic crosslinker. This combination resulted in formulation of extremely stable nanogels that could not be dissembled in the presence of DTT. It was postulated that the hydrophobic environment around the disulfide linker flanked between hydrophobic adamantane units did not allow efficient diffusion of the thiol-containing cleaving reagents. Hence a new hydrophilic crosslinker containing tetraethylene glycol (TEG) units was designed. Addition of a TEG unit between disulfide and adamantane moiety would overcome the steric and hydrophobic effects. Thus, second generation nanogels were fabricated using a disulfide-containing hydrophilic crosslinker and the βCD-grafted dextran polymer. As expected, these nanogels exhibited dissembly in the presence of DTT and glutathione. The effect of extent of βCD functionalization of dextran, polymer concentration and βCD to adamantane ratio on the size and reduction sensitivity of these nanogels were studied. An anti-cancer drug doxorubicin was loaded into the nanogels by either simple mixing or dialysis-based methods. The latter approach allowed control over size and produced stable nanogels with better drug loading capacites and loading efficiencies.
