524e Polyketals: A New Acid-Sensitive Biomaterial for Drug Delivery

Sungmun Lee, Stephen Yang, Michael Heffernan, and Niren Murthy. Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332

There is currently great interest in developing acid-sensitive materials for drug delivery because of their ability to hydrolyze in the acidic environment of phagosomes and release drugs into the cytoplasm. In this presentation, we introduce a new acid-sensitive polymer for drug delivery, poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK), which is ideal for treating inflammatory diseases because of its biocompatible degradation products. PCADK was synthesized using the acetal exchange reaction between 1,4-cyclohexanedimethanol and 2,2-dimethoxypropane. PCADK hydrolyzes into innocuous compounds, 1,4-cyclohexanedimethanol and acetone, which have FDA approval for human use. The hydrolysis half-life of PCADK is 24.1 days at pH 4.5 and over 4 years at pH 7.4, which is suitable for targeting chronic diseases. The therapeutic enzyme superoxide dismutase (SOD), which scavenges reactive oxygen species, was encapsulated into PCADK-based microparticles using a double emulsion procedure. Cell culture experiments demonstrated that PCADK-based microparticles significantly improved the ability of SOD to scavenge reactive oxygen species produced by macrophages. We anticipate the use of PCADK to treat a wide variety of chronic inflammatory diseases such as lung fibrosis, arthritis, and congestive heart failure.