Hydrogels with prolonged release of therapeutic antibody: Block junction chemistry modification of ‘ABA’ copolymers provides superior anticancer efficacy
In this study, we report a new series of vitamin E-functionalized ‘ABA’ triblock copolymers with carbamate block junction, which can form hydrogen-bonds. These polymers were synthesized via solvent- and catalyst-free nucleophilic addition between PEG-diamine and vitamin E-functionalized cyclic carbonate. The catalyst-free synthesis enabled an easy purification step and recycling of excess monomers. The polymers formed hydrogels through self-assembly by simply dissolving in aqueous solution. The hydrogel stiffness was easily tuned by varying polymer concentration, PEG molecular weight and number of vitamin E molecules. The triblock copolymer with one vitamin E molecule on each end of PEG (20 kDa) formed hydrogel at a concentration of 4.0 wt% and above. The hydrogel showed pronounced shear-thinning behavior, and was injectable. Particularly, the hydrogel formed with carbamate block junction was stiffer than that with carbonate block junction, and provided more sustained antibody release. The hydrogel with carbamate block junction was loaded with the anticancer antibody Herceptin, which suppressed tumor growth over a significantly longer period of time as compared to the Herceptin-loaded hydrogel with carbonate block junction (90 days vs. 40 days). This hydrogel has potential for use as matrix for sustained delivery of antibodies.