文摘
Polyketals, which can be biodegradable, have good biocompatibility, and are pH-sensitive, could have broad applicability in drug delivery and other biomedical applications. However, facile synthesis of high molecular weight polyketals is challenging, and short durations of drug release from polyketal particulate formulations limit their application in drug delivery. Here we report the synthesis of a di-isopropenyl ether monomer and its use to synthesize high molecular weight estradiol-polyketal conjugates by addition polymerization. Microparticles were prepared from the estradiol-polyketal conjugate, where estradiol was incorporated into the polymer backbone. The particles had high drug loading and significantly prolonged drug release. Release of estradiol from the drug-polyketal conjugate microparticles was acid-responsive, as evidenced by faster drug release at low pH and with co-incorporation of PLGA. Tissue reaction to the microparticles was benign in vivo. Polyketal drug conjugates are promising candidates for long-acting drug delivery systems to treat chronic diseases.