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    Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia

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    Nanoparticulate.pdf
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    Author
    Godfrey, Lisa
    Iannitelli, Antonio
    Garrett, Natalie L.
    Moger, Julian
    Imbert, Ian
    King, Tamara
    Porreca, Frank
    Soundararajan, Ramesh
    Lalatsa, Aikaterini
    Schätzlein, Andreas G.
    Uchegbu, Ijeoma F.
    Show allShow less
    Affiliation
    Univ Arizona, Coll Med, Dept Pharmacol
    Issue Date
    2017-11-27
    Keywords
    Nanoparticles
    Microparticles
    Chitosan amphiphiles
    Leucine(5)-enkephalin
    Intranasal
    Analgesia
    Brain delivery
    Delta opioid receptor
    
    Metadata
    Show full item record
    Publisher
    ELSEVIER SCIENCE BV
    Citation
    Godfrey, L., Iannitelli, A., Garrett, N. L., Moger, J., Imbert, I., King, T., Porreca, F. & Uchegbu, I. F. (2018). Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia. Journal of Controlled Release, 270, 135-144.
    Journal
    JOURNAL OF CONTROLLED RELEASE
    Rights
    © 2017 The Authors. Published by Elsevier B.V.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    The delivery of peptide drugs to the brain is challenging, principally due to the blood brain barrier and the low metabolic stability of peptides. Exclusive delivery to the brain with no peripheral exposure has hitherto not been demonstrated with brain quantification data. Here we show that polymer nanoparticles encapsulating leucine(5)-enkephalin hydrochloride (LENK) are able to transport LENK exclusively to the brain via the intranasal route, with no peripheral exposure and nanoparticle localisation is observed within the brain parenchyma. Animals dosed with LENK nanoparticles (NM0127) showed a strong anti-nociceptive response in multiple assays of evoked and on going pain whereas animals dosed intranasally with LENK alone were unresponsive. Animals did not develop tolerance to the anti-hyperalgesic activity of NM0127 and NM0127 was active in morphine tolerant animals. A microparticulate formulation of clustered nanoparticles was prepared to satisfy regulatory requirements for nasal dosage forms and the polymer nanoparticles alone were found to be biocompatible, via the nasal route, on chronic dosing.
    Note
    Open access article
    ISSN
    01683659
    PubMed ID
    29191784
    DOI
    10.1016/j.jconrel.2017.11.041
    Version
    Final published version
    Sponsors
    UK Engineering and Physical Sciences Research Council [EP/K502340/1]; Nanomerics Ltd. [NM12TSB-NPP]; Innovate UK [16939-124181]
    Additional Links
    http://linkinghub.elsevier.com/retrieve/pii/S0168365917310489
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.jconrel.2017.11.041
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    UA Faculty Publications

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