Poly(amino acid) Synthesis from 2,5-Diketopiperazines for Acid-Actuated Drug Release

Poly(amino acids) have enormous potential value as biomaterials owing to their inherent biocompatibility, chemical functionality, and biodegradability. However, current commercial poly(amino acid) use is somewhat limited due to production protocols that often include highly toxic phosgene in monomer synthesis. To circumvent this unfortunate predicament, the use of bio-renewable 2,5-diketopiperazines (2,5-DKPs) as cyclic monomers is proposed for poly(amino acid) synthesis. Amphiphilic block copolymers are produced by using poly(ethylene glycol) methyl ether (mPEG) as a macroinitiator, and pH-sensitive nanoparticles form capable of highly controlled, acid-actuated, doxorubicin release. This route to poly(amino acid) synthesis may facilitate the safe and economically viable use of key biodegradable polymers in both every day and high-value biomedical products, such as materials for stimuli-responsive drug delivery.