Tailor-Made Core-Multishell Nanocarriers for the Delivery of Cationic Analgesics to Inflamed Tissue

U50,488H (U50) is a kappa-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.