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Covalent incorporation and controlled release of active dexamethasone from injectable polyethylene glycol hydrogels

Authors

  • Deon Bezuidenhout,

    Corresponding author
    1. Cardiovascular Research Unit, Christiaan Barnard Department of Cardiothoracic Surgery, University of Cape Town, 203 Cape Heart Centre, Anzio Road, Observatory 7925, Cape Town, South Africa
    • Cardiovascular Research Unit, University of Cape Town, 203 Cape Heart Centre, Anzio Road, Observatory 7925, Cape Town, South Africa
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  • Anel Oosthuysen,

    1. Cardiovascular Research Unit, Christiaan Barnard Department of Cardiothoracic Surgery, University of Cape Town, 203 Cape Heart Centre, Anzio Road, Observatory 7925, Cape Town, South Africa
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  • Neil Davies,

    1. Cardiovascular Research Unit, Christiaan Barnard Department of Cardiothoracic Surgery, University of Cape Town, 203 Cape Heart Centre, Anzio Road, Observatory 7925, Cape Town, South Africa
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  • Lage Ahrenstedt,

    1. Cardiovascular Research Unit, Christiaan Barnard Department of Cardiothoracic Surgery, University of Cape Town, 203 Cape Heart Centre, Anzio Road, Observatory 7925, Cape Town, South Africa
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  • Stephan Dobner,

    1. Cardiovascular Research Unit, Christiaan Barnard Department of Cardiothoracic Surgery, University of Cape Town, 203 Cape Heart Centre, Anzio Road, Observatory 7925, Cape Town, South Africa
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  • Peter Roberts,

    1. Cardiovascular Research Unit, Christiaan Barnard Department of Cardiothoracic Surgery, University of Cape Town, 203 Cape Heart Centre, Anzio Road, Observatory 7925, Cape Town, South Africa
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  • Peter Zilla

    1. Cardiovascular Research Unit, Christiaan Barnard Department of Cardiothoracic Surgery, University of Cape Town, 203 Cape Heart Centre, Anzio Road, Observatory 7925, Cape Town, South Africa
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  • How to cite this article: Bezuidenhout D, Oosthuysen A, Davies N, Ahrenstedt L, Dobner S, Roberts P, Zilla P. 2013. Covalent incorporation and controlled release of active dexamethasone from injectable polyethylene glycol hydrogels. J Biomed Mater Res Part A 2013:101A:1311–1318.

Abstract

Dexamethasone (Dex) is used in a wide range of applications, but may have undesirable systemic side effects. A number of techniques have thus been developed to deliver the substance locally. In this study, dexamethasone was acrylated, pegylated, and tethered to hydrolytically degradable (acrylate based) and nondegradable (vinyl sulfone based) polyethylene glycol hydrogels by nucleophilic addition. Hydrogel swelling, drug elution and drug activity were followed over an extended period in vitro. Nondegradable gels were stable for more than a year, while degradable gels showed increasing swelling ratios due to degradation that resulted in disintegration after ∼12 days. Near-linear (zero order) release could be achieved in some cases with the degradable gels, while release from the nondegradable gels approximated first order initial release kinetics. Significantly delayed release was observed in all cases where the Dex was linked to the gels, when compared with controls where the drug was merely physically incorporated. Eluates from the gels containing the tethered drug showed high levels of activity for extended time periods, while the activity of the eluates from gels containing nonbound dexamethasone decreased rapidly within the first few days. Dexamethasone can thus be incorporated using nucleophilic addition chemistry to produce gels that are capable of sustained release of the active drug. The methodology is applicable to a variety of drugs that contain hydroxyl groups. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

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