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Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow-Focusing Device for Controlled Drug Delivery

Authors

  • Qiaobing Xu,

    1. Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachussets Avenue, Cambridge, MA 02139 (USA)
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    • These authors contributed equally to the work.

  • Michinao Hashimoto,

    1. Department of Chemistry and Chemical Biology, Harvard University 12 Oxford Street, Cambridge, MA 02138 (USA)
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    • These authors contributed equally to the work.

  • Tram T. Dang,

    1. Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachussets Avenue, Cambridge, MA 02139 (USA)
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  • Todd Hoare,

    1. Department of Chemical Engineering, McMaster University 1280 Main St. W, Hamilton, ON (Canada)
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  • Daniel S. Kohane,

    1. Anesthesiology/Critical Care Medicine, Children's Hospital Boston 300 Longwood Avenue, Boston, MA 02115 (USA)
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  • George M. Whitesides,

    1. Department of Chemistry and Chemical Biology, Harvard University 12 Oxford Street, Cambridge, MA 02138 (USA)
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  • Robert Langer,

    1. David H. Koch Institute for Integrative Cancer Research, MIT 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
    2. Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachussets Avenue, Cambridge, MA 02139 (USA)
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  • Daniel G. Anderson

    Corresponding author
    1. David H. Koch Institute for Integrative Cancer Research, MIT 77 Massachusetts Avenue, Cambridge, MA 02139 (USA)
    • David H. Koch Institute for Integrative Cancer Research, MIT 77 Massachusetts Avenue, Cambridge, MA 02139 (USA).
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Abstract

Degradable microparticles have broad utility as vehicles for drug delivery and form the basis of several therapies approved by the US Food and Drug Administration. Conventional emulsion-based methods of manufacturing produce particles with a wide range of diameters (and thus kinetics of release) in each batch. This paper describes the fabrication of monodisperse, drug-loaded microparticles from biodegradable polymers using the microfluidic flow-focusing (FF) devices and the drug-delivery properties of those particles. Particles are engineered with defined sizes, ranging from 10 µm to 50 µm. These particles are nearly monodisperse (polydispersity index = 3.9%). A model amphiphilic drug (bupivacaine) is incorporated within the biodegradable matrix of the particles. Kinetic analysis shows that the release of the drug from these monodisperse particles is slower than that from conventional methods of the same average size but a broader distribution of sizes and, most importantly, exhibit a significantly lower initial burst than that observed with conventional particles. The difference in the initial kinetics of drug release is attributed to the uniform distribution of the drug inside the particles generated using the microfluidic methods. These results demonstrate the utility of microfluidic FF for the generation of homogenous systems of particles for the delivery of drugs.

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