The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.

• MeSH
• akrylamidy chemie   farmakologie   aplikace a dávkování   MeSH
• antiflogistika farmakologie   aplikace a dávkování   chemie   MeSH
• Aspirin * aplikace a dávkování   farmakologie   chemie   MeSH
• cyklooxygenasy metabolismus   MeSH
• inhibitory cyklooxygenasy farmakologie   aplikace a dávkování   chemie   MeSH
• léky s prodlouženým účinkem * MeSH
• mediátory zánětu metabolismus   MeSH
• myši MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• polymery * chemie   aplikace a dávkování   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug (NSAID) commonly used in the treatment of pain, fever and inflammation. However, the administration of IBU in its free carboxylic acid form is strongly dependent on its limited solubility in aqueous solution. This mandates for an increased drug concentration to reach the therapeutic window, and promotes the alternative use of IBU sodium salt, even if this latter form poses significant constraints in terms of tunable release due to its uncontrolled and rapid diffusion. A potential solution is represented by oral administration through physical encapsulation of ibuprofen in designed carriers, despite this route limits the application of this therapeutic agent. In this work, we propose the covalent tethering of ibuprofen to a hydrogel matrix via esterification reaction. Exploiting the cleavability of the ester bond under physiological conditions, we propose a controlled drug delivery system where the whole drug payload can be released, thus overcoming the questioned aspects of over-dosage and solubility-dependent administration. In particular, we tested the biological activity of cleaved ibuprofen in terms of cyclooxygenase inhibition, reporting that chemical tethering did not alter the efficiency of the NSAID. Moreover, due to the sol-gel transition of the hydrogel matrix, these ibuprofen-functionalized hydrogels could be used as injectable tools in several clinical scenarios, performing a localized drug release and opening advanced avenues for in situ treatments.

• MeSH
• akrylové pryskyřice chemie   MeSH
• aplikace orální MeSH
• cyklooxygenasy metabolismus   MeSH
• enzymatické testy MeSH
• hydrogely chemie   MeSH
• ibuprofen aplikace a dávkování   farmakokinetika   MeSH
• inhibitory cyklooxygenasy aplikace a dávkování   farmakokinetika   MeSH
• léky s prodlouženým účinkem aplikace a dávkování   farmakokinetika   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nosiče léků chemie   MeSH
• propylenglykoly chemie   MeSH
• rozpustnost MeSH
• sefarosa chemie   MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• chinony aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• cyklooxygenasy metabolismus   MeSH
• dinoproston biosyntéza   MeSH
• finanční podpora výzkumu jako téma MeSH
• fytoterapie MeSH
• inhibiční koncentrace 50 MeSH
• inhibitory cyklooxygenasy aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• membránové proteiny MeSH
• Nigella sativa MeSH
• rostlinné extrakty aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• thymol aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH