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Polymer nanotherapeutics with the controlled release of acetylsalicylic acid and its derivatives inhibiting cyclooxygenase isoforms and reducing the production of pro-inflammatory mediators
Autoři | |
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Rok publikování | 2024 |
Druh | Článek v odborném periodiku |
Časopis / Zdroj | International Journal of Pharmaceutics |
Fakulta / Pracoviště MU | |
Citace | |
www | https://www.sciencedirect.com/science/article/pii/S0378517324009761 |
Doi | http://dx.doi.org/10.1016/j.ijpharm.2024.124742 |
Klíčová slova | Drug delivery; HPMA; Nanotherapeutics; Inflammation; Acetylsalicylic acid; Salicylic acid hydrazide |
Popis | 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 esterbound 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. |