Switchable release nano-reservoirs for co-delivery of drugs via a facile micelle-hydrogel composite

Precise and controlled drug delivery systems are required to facilitate effective therapeutics. To address this need, we devised a micelle-hydrogel composite based on amphiphilic polypeptides as a general carrier model for the switchable and controlled release of dual drugs. Two different di-block polypeptides, poly(L-lysine-b-L-phenylalanine) and poly(L-glutamic acid-b-L-phenylalanine) (PGA-PPA), were synthesized to form distinct self-assembling micellar systems that were loaded with curcumin and amphotericin B, respectively, as model drugs. The drug-loaded micellar mixture was crosslinked utilizing the pendant amino groups of the L-lysine side chains via genipin to yield a micelle-hydrogel composite with PGA-PPA micelles trapped in an interlinked hydrogel system. This composite allowed for controlled multiphasic drug release and could be effectively tuned to moderate the pace and amount of drug release and be easily regulated to switch the drug release kinetics over a range of simple factors such as change in pH, cross-linking density, and composition.