In situ forming, resorbable graft copolymer hydrogels providing controlled drug release

Authors

  • Derek J. Overstreet,

    1. Center for Interventional Biomaterials, School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287-9709
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  • Richard Huynh,

    1. Center for Interventional Biomaterials, School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287-9709
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  • Keith Jarbo,

    1. Orthopaedic Residency, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006
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  • Ryan Y. McLemore,

    1. Orthopaedic Residency, Banner Good Samaritan Medical Center, Phoenix, Arizona 85006
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  • Brent L. Vernon

    Corresponding author
    1. Center for Interventional Biomaterials, School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287-9709
    • School of Biological and Health Systems Engineering, Center for Interventional Biomaterials, Arizona State University, Tempe, Arizona 85287-9709
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  • How to cite this article: Overstreet DJ, Huynh R, Jarbo K, McLemore RY, Vernon BL. 2013. In situ forming, resorbable graft copolymer hydrogels providing controlled drug release. J Biomed Mater Res Part A 2013:101A:1437–1446.

Abstract

In situ forming hydrogels are promising drug delivery vehicles due to their ease of delivery as liquids and their ability to be used in sites with irregular geometries. In this work, we report on in situ forming, resorbable hydrogels based on N-isopropylacrylamide (NIPAAm) as a fluid-like controlled release gel. These gels are the first resorbable NIPAAm-based gels providing controlled release without relying on affinity between the drug and device. Therefore, these gels provide a more flexible delivery system which can be used to deliver any drug at a controlled rate. The polymers contain repeat units of NIPAAm with (R)-α-Acryloyloxy-β,β-dimethyl-γ-butyrolactone (DBLA) and varying amounts of hydrophilic Jeffamine® M-1000 acrylamide (JAAm) grafts. The graft copolymer architecture allows the water content of the hydrogels to be tuned over a wide range while keeping the initial gelation temperature below body temperature. Incorporation of JAAm in the polymers led to greater water content, faster gel degradation, and reduced burst release. Sustained release of the antimicrobial drugs cefazolin and vancomycin (over about 5 and 7 days, respectively) was observed from gels containing an intermediate amount of grafts which combined reduced phase separation with a degradation time of 40 days. The degradation byproducts of one hydrogel formulation were cytocompatible to NIH 3T3 fibroblasts at concentrations up to 2.5 wt %. This class of terpolymer hydrogels is a promising local delivery system for a wide variety of drugs, particularly for applications involving irregular geometries such as implant interfaces. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

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