(600b) Protease-Sensitive Polymer Vesicles for Drug Delivery

Stimuli-responsive polymersomes or polymer vesicles are capable of encapsulating and releasing their load when suitable signals are present. Several internal and external stimuli have been used such as pH, temperature, light, redox potential and magnetic field. Here we report a novel protease-cleavable amphiphilic block copolymer which self-assembles into protease-responsive, nano-sized polymeric vesicles. Each self-assembling unit consists of a peptide substrate (alanine-alanine-alanine-phenylalanine) labile to chymotrypsin linked between polyethylene glycol (PEG) and polycaprolactone (PCL). The hydrophilic content of the block copolymer is made to be 24% in order to form adopt the vesicle structure. Nano-precipitation followed by membrane extrusion produced polymer vesicles with an average diameter of 144 nm (as detected by dynamic light scattering). Since the cleavage site is located between the PEG and PCL blocks, hydrophilic contents of the cleavage products become 100% and 0% for PEG and PCL block respectively upon proteolysis. When incubated with chymotrypsin, the vesicles are disrupted as shown by TEM images: poration on the membrane and formation of larger vesicles are observed. Hydrophilic fluorescent dye is encapsulated and the release is triggered by the incubation with chymotrypsin. The system has the potential of tailoring release to different protease expression associated with pathological conditions, such as in inflammatory diseases and cancer.