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    Impact of Excipients on Stability of Polymer Microparticles for Autoimmune Therapy.

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    Author
    Gosselin, Emily A
    Noshin, Maeesha
    Black, Sheneil K
    Jewell, Christopher M
    Date
    2021-02-11
    Journal
    Frontiers in Bioengineering and Biotechnology
    Publisher
    Frontiers Media S.A.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3389/fbioe.2020.609577
    Abstract
    Therapies for autoimmune diseases such as multiple sclerosis and diabetes are not curative and cause significant challenges for patients. These include frequent, continued treatments required throughout the lifetime of the patient, as well as increased vulnerability to infection due to the non-specific action of therapies. Biomaterials have enabled progress in antigen-specific immunotherapies as carriers and delivery vehicles for immunomodulatory cargo. However, most of this work is in the preclinical stage, where small dosing requirements allow for on-demand preparation of immunotherapies. For clinical translation of these potential immunotherapies, manufacturing, preservation, storage, and stability are critical parameters that require greater attention. Here, we tested the stabilizing effects of excipients on the lyophilization of polymeric microparticles (MPs) designed for autoimmune therapy; these MPs are loaded with peptide self-antigen and a small molecule immunomodulator. We synthesized and lyophilized particles with three clinically relevant excipients: mannitol, trehalose, and sucrose. The biophysical properties of the formulations were assessed as a function of excipient formulation and stage of addition, then formulations were evaluated in primary immune cell culture. From a manufacturing perspective, excipients improved caking of lyophilized product, enabled more complete resuspension, increased product recovery, and led to smaller changes in MP size and size distribution over time. Cocultures of antigen-presenting cells and self-reactive T cells revealed that MPs lyophilized with excipients maintained tolerance-inducing function, even after significant storage times without refrigeration. These data demonstrate that excipients can be selected to drive favorable manufacturing properties without impacting the immunologic properties of the tolerogenic MPs. © Copyright © 2021 Gosselin, Noshin, Black and Jewell.
    Rights/Terms
    Copyright © 2021 Gosselin, Noshin, Black and Jewell.
    Keyword
    autoimmunity
    excipient
    formulation
    immunotherapy
    lyophilization
    multiple sclerosis
    nanotechnology
    stability
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14863
    ae974a485f413a2113503eed53cd6c53
    10.3389/fbioe.2020.609577
    Scopus Count
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    UMB Open Access Articles 2021

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