Protein encapsulation in and release from monodisperse double-wall polymer microspheres

Authors

  • Yujie Xia,

    1. Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, Illinois 61801
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  • Qingxing Xu,

    1. Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, Illinois 61801
    2. Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117576, Singapore
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  • Chi-hwa Wang,

    1. Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117576, Singapore
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  • Daniel W. Pack

    Corresponding author
    1. Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, Illinois 61801
    • Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, Illinois 61801. Telephone: +859-218-0907; Fax: +859-257-7585
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Abstract

Biodegradable polymer double-wall microspheres (DWMS) are promising vehicles for macromolecular therapeutics such as proteins and peptides. Using precision particle fabrication (PPF) technology, uniform DWMS with outer diameter approximately 55 μm were fabricated comprising poly(lactide-co-glycolide) cores encapsulating bovine serum albumin (BSA) and approximately 10 μm thick, drug-free, poly(lactic acid) (PLA) shells of varying PLA molecular weight. Also, monolithic single-wall microspheres (SWMS) were fabricated to mimic the BSA-loaded core. The use of relatively fast-extracting ethyl acetate and slowly extracting dichloromethane as shell- and core-phase solvents, respectively, was found to produce DWMS with well-defined core–shell structure, high BSA encapsulation efficiency, and the desired localization of protein in the particle core. Initial protein distribution, particle erosion, and in vitro protein release from DWMS and SWMS were examined. The presence of a BSA-free shell in DWMS decreased the protein release rate and extended the duration of release from approximately 50 days to 70–80 days, demonstrating the capacity of such DWMS to provide enhanced control of protein delivery rates. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1601–1609, 2013

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