Tailor‐Made Core‐Multishell Nanocarriers for the Delivery of Cationic Analgesics to Inflamed Tissue. Issue 5 (26th February 2019)

• Record Type: Journal Article
• Authors: Unbehauen, Michael L.; Łabuz, Dominika; Schwarzl, Richard; Moré, Sam; Netz, Roland R.; Stein, Christoph; Machelska, Halina; Haag, Rainer
• Is Part Of: Advanced therapeutics. Volume 2:Issue 5(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-02-26
• Subjects: analgesia -- CMS nanocarriers -- drug delivery -- pH responsiveness; Therapeutics -- Periodicals; Pharmaceutical technology -- Periodicals; Pharmacogenetics -- Periodicals; 615.5
• DOI: 10.1002/adtp.201900007
• Languages: English
• ISSNs: 2366-3987

Abstract

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. Abstract : U50, 488H (U50) is a κ‐opioid receptor agonist exerting analgesia in animal pain models . Here, tailor‐made core‐multishell (CMS) nanocarriers are presented that interact with U50 non‐covalently. Despite their small size, they exhibit a pH‐dependent retention effect in in vitro release studies. Experiments in the in vivo rat model of inflammatory pain show a prolonged analgesia.