Polyketal Microparticles: A New Delivery Vehicle for Superoxide Dismutase

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• 作者：Sungmun Lee ; Stephen C. Yang ; Michael J. Heffernan ; W. Robert Taylor ; Niren Murthy
• 刊名：Bioconjugate Chemistry
• 出版年：2007
• 出版时间：January 2007
• 年：2007
• 卷：18
• 期：1
• 页码：4 - 7
• 全文大小：148K
• 年卷期：v.18,no.1(January 2007)
• ISSN：1520-4812

文摘

There is currently great interest in developing microparticles that can enhance the delivery of proteins tomacrophages. In this communication, we present a new acid-sensitive polymer for drug delivery, poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK). PCADK is designed to hydrolyze, after phagocytosis bymacrophages, in the acidic environment of the phagosome and enhance the intracellular delivery of phagocytosedtherapeutics. Other key attributes of PCADK for drug delivery are its well-characterized degradation productsand straightforward synthesis. PCADK hydrolyzes into 1,4-cyclohexanedimethanol, a compound used in foodpackaging, and acetone, a compound on the FDA GRAS list. PCADK was synthesized using the acetal exchangereaction between 1,4-cyclohexanedimethanol and 2,2-dimethoxypropane, and could be obtained on a multigramscale in one step. The hydrolysis kinetics of the ketal linkages in PCADK were measured by ¹H NMR and weredetermined to be pH-sensitive, having a half-life of 24.1 days at pH 4.5 and over 4 years at pH 7.4. The therapeuticenzyme 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 dramatically improved the ability of SOD to scavenge reactive oxygen species produced bymacrophages. We anticipate numerous applications of PCADK in drug delivery, based on its acid sensitivity,well-characterized degradation products, and straightforward synthesis.