Degradable polymers are an emerging research interest. The innovation of new degradable polymers for biomedical applications is challenging due to strict demands including nontoxicity of polymers and degraded products, complete degradation to avoid polymer residues in the body, and other suitable properties. Here, we demonstrate a series of degradable polymers for sustained-release drug applications synthesized by the alternating copolymerization of cyclic anhydrides and Schiff bases. In addition to common feedstocks, the copolymerization is versatile and catalyst-free, affording polymers incorporating cyclic topologies and in-chain ester and peptoid groups. Particularly, the polymers exhibit self- and autodegradation without any trigger, which is distinct from remaining degradation mechanisms. The degradation performance is widely regulated by the polymer structure and external temperature, resulting in complete degradation from a few hours to several months. Owing to their unique properties, the polymers are approved for biomedical applications, as revealed soundly through cell viability assay, in vitro and in vivo drug release.
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