Abstract
Cancer aggressiveness and metastases represent a major cause of death worldwide. Cyclooxygenase-2 (COX-2), and its metabolites significantly influence the tumor development, and metastatic processes. The design and synthesis of prodrugs intended for nonsteroidal anti-inflammatory drugs (NSAIDs) have garnered considerable attention from medicinal chemists, particularly in the last decade. A pH-sensitive drug delivery carrier based on TEG-derivatized ibuprofen Ibu-TEG was synthesized to serve as a dual-delivery system for anti-inflammatory and anticancer agents. The successful synthesis was confirmed through various spectroscopic techniques. This amphiphilic and biodegradable prodrug was self-assembled into micellar nanoparticles (Ibu-TEG-NPs). Their surface was subsequently modified with biocompatible molecules, chitosan (Ibu-TEG-NPs-CHI), and poly-dopamine (Ibu-TEG-NPs-PDA), to enhance the drug efficacy and thermal stability. As-prepared NPs were characterized through FT-IR, DLS, TGA, AFM, and SEM. These surface-modified NPs were significantly active against ROS and NO generation, and showed a lower IC50 value than ibuprofen. Moreover, Ibu-TEG-NPs, Ibu-TEG-NPs-CHI, and Ibu-TEG-NPs-PDA revealed significant therapeutic activity against lung–NCI–H460, and hepato-HepG2 cancer cell lines, demonstrating low IC50 values.
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