Low solubility of potent (anti-cancer) drugs is a major driving force for the development of non-cytotoxic, stimuli-responsive nanocarriers, including systems based on amphiphilic block copolymers. In this regard, we investigated the potential of polyacrylates and polyacrylamides with pending ketal moieties to form responsive drug nanocarriers. Block copolymers were successfully synthesized by sequential reversible addition-fragmentation chain transfer (RAFT) polymerization, in which we combined a hydrophilic polymer block (either a synthetic polyacrylate/polyacrylamide or a natural polysaccharide) with a ketal-containing polymer block. By varying the nature of the ketal system, block copolymers with temperature-responsive properties within a physiologically relevant window are obtained. Above the phase transition temperature, the block copolymer self-assemble into micellar or vesicular nanostructures. The ketal group is acid-responsive and affords disassembly of the nanoparticles. The hydrophobic interior of the formed nanostructures can be loaded with hydrophobic dyes and drug molecules. Flow cytometry and confocal microscopy showed dose-dependent, active cellular uptake of the particles in vitro. The block copolymers showed no intrinsic in vitro cytotoxicity, whilst loaded with paclitaxel (PTX), a significant decrease in cell viability was observed comparable or better than the two commercial PTX nanoformulations Abraxane and Genexol-PM at equal PTX dose.

Ketal-containing poyacrylates and polyacrylamides as building blocks for multi-responsive nanomedicines

249th National Meeting (2015)

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