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Tailor‐Made Core‐Multishell Nanocarriers for the Delivery of Cationic Analgesics to Inflamed Tissue
Author(s) -
Unbehauen Michael L.,
Łabuz Dominika,
Schwarzl Richard,
Moré Sam,
Netz Roland R.,
Stein Christoph,
Machelska Halina,
Haag Rainer
Publication year - 2019
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.201900007
Subject(s) - nanocarriers , agonist , in vivo , pharmacology , surface modification , drug delivery , chemistry , materials science , nanotechnology , drug , biomedical engineering , medicine , receptor , biochemistry , biology , microbiology and biotechnology
Abstract U50,488H (U50) is a κ‐opioid receptor agonist exerting effective analgesia in animal pain models. Yet, side effects such as sedation and depression‐like symptoms mediated in the brain limit its therapeutic potential. In this study, tailor‐made core‐multishell (CMS) nanocarriers are presented containing U50 that, despite their small size, exhibit a pH‐dependent retention effect via non‐covalent interactions with the drug. The nanocarriers and their non‐functionalized counterparts are characterized regarding their release properties in vitro, including a theoretical modeling of the release parameters which show the beneficial features of the additional functionalization. Finally, the U50‐containing nanocarriers are tested in an in vivo rat model of inflammatory pain, with the results showing prolonged analgesic effect.