Naproxen Sodium

Naproxen is a reversible, cyclooxygenase (COX) inhibitor. It is part of the arylacetic acid group of non-steroidal anti-inflammatory drugs (NSAIDs). The two main isoforms of COX, COX-1 and COX-2, are enzymes that catalyze the first step in the conversion of free arachidonic acid to prostaglandins, which have physiological actions relating to perception of pain, regulation of body temperature, initiation of inflammatory reactions, blood clotting, and other roles in normal cardiovascular function. Naproxen preferentially inhibits COX-1; however, it also blocks COX-2 to a lesser extent. Inhibition of prostanoid biosynthesis, especially the decreased production of prostaglandins G and H, results in effective control of pain arising from a wide variety of causes.

Fig. 1 The Pharmacological Mechanism of Action of NSAIDs. (Stoev S N, et al. 2021)

Non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen are widely used to treat inflammatory conditions and pain. NSAIDs are also associated with gastric ulcers due to their suppression of prostaglandin and induction of oxidative stress. Researchers investigated whether the polyvinyl alcohol (PVA) capped naproxen sodium–magnesium oxide nanoparticle (NPRS-MgO NP) formulation has lower gastric toxicity than the conventional naproxen sodium (NPRS) drug. Mice received one of the following treatments: NPRS, coated nanoformulation (CNF), uncoated nanoformulation (UNF), MgO NPs, or control. The administration of NPRS resulted in severe gastric ulceration and significantly increased oxidative stress markers (ROS, MDA) and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). This occurred alongside the depletion of antioxidants (CAT, POD, SOD, GSH). Histological analysis of gastric mucosa revealed epithelial cell disruption and inflammatory cell infiltration, while immunohistochemical analysis of COX-2, i-NOS, and caspase-3 expression was upregulated. The application of CNF and UNF formulations resulted in a lack of mucosal damage and was accompanied by a restoration of antioxidant and anti-inflammatory processes with normalization of tissue architecture and apoptotic markers. The gastroprotective effect of nanoformulations was ascribed to the sustained release of naproxen, which is likely to alleviate the local toxicity and oxidative damage that causes ulcers. CNF had a superior effect to UNF, which may be due to the stability imparted by the PVA polymer coating. Overall, the study demonstrated that NPRS nanoformulations have a lower gastric toxicity profile than the conventional NSAID, with PVA-coated NPRS-MgO NP significantly reducing side effects while maintaining therapeutic efficacy.

Fig. 2 Schematics of naproxen sodium nanoparticles. (Razzaq A, Qureshi I Z. 2022)