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Background: In the randomized, phase 3, SUSA‐301 trial, celecoxib‐tramadol co‐crystal (CTC) provided significantly greater analgesia compared with celecoxib, tramadol, or placebo in adults with acute, moderate‐to‐severe, postoperative pain. This post hoc, secondary analysis further evaluated the use of rescue medication and the incidence of treatment‐emergent adverse events (TEAEs). Methods: Patients (N = 637) were randomized 2:2:2:1 to receive oral CTC 200 mg twice daily (BID; n = 184), tramadol 50 mg four times daily (QID; n = 183), celecoxib 100 mg BID (n = 181), or placebo QID (n = 89). Post hoc analyses were conducted on the use of rescue medications up to 4 and 48 h post‐study drug dose, stratified by baseline pain intensity (moderate/severe), and on the incidence of TEAEs, stratified by rescue medication use. Results: A significantly lower proportion of patients received any rescue medication within 4 h post‐study dose with CTC (49.5%) versus tramadol (61.7%, p = 0.0178), celecoxib (65.2%, p = 0.0024), and placebo (75.3%, p = 0.0001); this was also seen for oxycodone use. Fewer patients in the CTC group received ≥3 doses of rescue medication compared with the other groups, irrespective of baseline pain intensity. In patients who did not receive opioid rescue medication, CTC was associated with a lower incidence of nausea and vomiting TEAEs versus tramadol alone. In patients who received rescue oxycodone, the incidence of nausea was similar in the CTC and tramadol groups, and higher versus celecoxib and placebo. Conclusion: Celecoxib‐tramadol co‐crystal was associated with reduced rescue medication use and an acceptable tolerability profile compared with tramadol or celecoxib alone in adults with acute, moderate‐to‐severe, postoperative pain. [ABSTRACT FROM AUTHOR]

This study aimed to develop and evaluate a novel herbal gel formulation containing celecoxib and bioactive compounds of Salai Guggul for effective pain management. Celecoxib, a selective COX-2 inhibitor with anti-inflammatory and analgesic properties, was combined with menthol, safflower oil, and Salai Guggul extract to enhance therapeutic efficacy through synergistic effects. Three gel formulations (CHG I, CHG II, and CHG III) were prepared using varying concentrations of key excipients and evaluated for physicochemical properties, including pH, viscosity, extrudability, spreadability, and in vitro drug diffusion. All formulations exhibited favorable properties with pH values near skin compatibility, acceptable viscosity, and superior extrudability and spreadability. In vitro drug diffusion studies revealed that CHG I provided the highest drug release (97.27%) over 240 minutes. The study demonstrated the potential of this herbal gel formulation as a promising topical treatment for pain management, offering improved skin permeation and prolonged drug release. [ABSTRACT FROM AUTHOR]

In addition to residual tumor cells, surgery-induced inflammation significantly contributes to tumor recurrence and metastasis by recruiting polymorphonuclear neutrophils (PMNs) and promoting their involvement in tumor cell proliferation, invasion and immune evasion. Efficiently eliminating residual tumor cells while concurrently intervening in PMN function represents a promising approach for enhanced postoperative cancer treatment. Here, a chitosan/polyethylene oxide electrospun fibrous scaffold co-delivering celecoxib (CEL) and doxorubicin-loaded tumor cell-derived microparticles (DOX-MPs) is developed for postoperative in-situ treatment in breast cancer. This implant (CEL/DOX-MPs@CP) ensures prolonged drug retention and sustained release within the surgical tumor cavity. The released DOX-MPs effectively eliminate residual tumor cells, while the released CEL inhibits the function of inflammatory PMNs, suppressing their promotion of residual tumor cell proliferation, migration and invasion, as well as remodeling the tumor immune microenvironment. Importantly, the strategy is closely associated with interference in neutrophil extracellular trap (NET) released from inflammatory PMNs, leading to a substantial reduction in postoperative tumor recurrence and metastasis. Our results demonstrate that CEL/DOX-MPs@CP holds great promise as an implant to enhance the prognosis of breast cancer patients following surgery. [Display omitted] • CEL/DOX-MPs@CP exhibit prolonged drug retention within surgical tumor cavity. • CEL/DOX-MPs@CP efficiently eliminate residual tumor cells. • CEL/DOX-MPs@CP inhibit PMN-promoted tumor cell behavior. • CEL/DOX-MPs@CP efficiently inhibit the tumor recurrence and metastasis. [ABSTRACT FROM AUTHOR]

NLRP1 is predominantly overexpressed in breast cancer tissue, and the evaluated activation of NLRP1 inflammasome is associated with tumor growth, angiogenesis, and metastasis. Therefore, targeting NLRP1 activation could be a crucial strategy in anticancer therapy. In this study, we investigated the hypothesis that NLRP1 pathway may contribute to the cytotoxic effects of celecoxib and nimesulide in MDA-MB-231 cells. First of all, IC50 values and inhibitory effects on the colony-forming ability of drugs were evaluated in cells. Then, the alterations in the expression levels of NLRP1 inflammasome components induced by drugs were investigated. Subsequently, the release of inflammatory cytokine IL-1β and the activity of caspase-1 in drug-treated cells were measured. According to our results, celecoxib and nimesulide selectively inhibited the viability of MDA-MB-231 cells. These drugs remarkably inhibited the colony-forming ability of cells. The expression levels of NLRP1 inflammasome components decreased in celecoxib-treated cells, accompanied by decreased caspase-1 activity and IL-1β release. In contrast, nimesulide treatment led to the upregulation of the related protein expressions with unchanged caspase-1 activity and increased IL-1β secretion. Our results indicated that the NLRP1 inflammasome pathway might contribute to the antiproliferative effects of celecoxib in MDA-MB-231 cells but is not a crucial mechanism for nimesulide. [ABSTRACT FROM AUTHOR]

Given that (hetero)aryl carboxylic acids are inexpensive materials available in a great variety from commercial and natural resources or synthesis, the strategies enabling their use as starting materials for preparing fine chemicals are highly sought after. Here we report a photoinduced Cu(II)‐mediated protocol converting (hetero)aryl carboxylic acids into (hetero)aryl thianthrenium salts, high value‐added building blocks that can undergo various subsequent transformations, creating an attractive two‐step pathway for the divergent functionalization of these ubiquitous starting materials. The excellent compatibility of the method is shown by preparing a broad range of sterically and electronically varied (hetero)aryl thianthrenium salts, including derivatives of pharmaceuticals, such as ataluren, celecoxib, flavoxate, probenecid, repaglinide, and tamibarotene. The syntheses of 13 C‐labeled probenecid and bioisosteres of ataluren as well as the unconventional modifications of celecoxib and flavoxate, illustrate the synthetic potential of the strategy. Mechanistic studies are in line with a reaction occurring through a photoinduced ligand‐to‐metal charge transfer (LMCT) of Cu(II)‐arylcarboxylates, enabling radical decarboxylative carbometallation to form arylcopper(II) intermediates that in turn react with thianthrene to form the product. Noteworthy, the susceptibility of aryl thianthrenium salts to photodegradation is overcome by a Cu(I)‐driven salvage loop, which continuously intercepts the transiently formed radicals and regenerates the products. [ABSTRACT FROM AUTHOR]