Search Results (750)

Nonsteroidal anti-inflammatory drugs (NSAIDs) can exacerbate urticaria and/or angioedema in up to 30% of patients with chronic urticaria (CU), representing a distinct subtype characterized by heightened inflammation and leukotriene-driven pathophysiology. MicroRNAs (miRNAs) are post-transcriptional regulators that modulate immune and inflammatory responses. This study aimed to identify differentially expressed miRNAs (DEMs) according to NSAID hypersensitivity status and to elucidate their molecular networks in CU. Serum miRNA profiles were analyzed in 14 NSAID-exacerbated CU (NECU) and 16 NSAID-tolerant CU (NTCU) patients using an Affymetrix GeneChip^® miRNA 4.0 Array. DEMs were identified (fold difference > 1.5, p < 0.05), and validated targets were retrieved from the multiMiR database for network construction and Gene Ontology enrichment analyses. NECU patients exhibited a higher frequency of angioedema and systemic corticosteroid use than NTCU patients. Eight DEMs were identified, including upregulated miR-5001-5p, miR-4270, and miR-6869-5p, and downregulated miR-6511b-5p, miR-2277-5p, and miR-378h in NECU. Network integration revealed AGO2-BTG2-LMNB2, NFIC-ZZZ3, and NUFIP2-GLG1 as central clusters, implicating dysregulation of mRNA decay and inflammatory signaling pathways. Reduced miR-6511b-5p expression may derepress BRG1, enhancing chromatin accessibility for inflammatory and leukotriene-synthetic genes. Distinct miRNA signatures differentiate NECU from NTCU, implying a miR-5001-5p/miR-6511b-5p–mRNA decay axis that links impaired post-transcriptional regulation with leukotriene-driven inflammation in CU. These findings highlight candidate miRNAs as potential biomarkers for disease endotyping and therapeutic stratification. Full article

Background and Objectives: Hysteroscopy has become the “gold standard” in assessing uterine cavity abnormalities, and currently it can be performed in an “office setting”. Although office hysteroscopy has a better level of comfort than operative hysteroscopy, pain is a common concern. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for pre-procedure analgesia, but they may cause gastrointestinal side effects. Paracetamol offers to be a safer alternative, but its efficacy in this setting is limited. This study aimed to compare the efficacy and safety of oral paracetamol with oral ketoprofen for pain management during office hysteroscopy. Materials and Methods: Double-blind, parallel-group, randomized controlled trial conducted at a single hysteroscopy center in Jakarta, Indonesia, over a 2-year period. Sixty women undergoing office hysteroscopy were randomized (1:1) to receive paracetamol 1000 mg orally or ketoprofen 100 mg orally 1 h before the procedure. Results: All participants completed the trial and were included in the analysis. The median visual analog score (VAS) during the procedure was 2 (range 0–8) in the paracetamol group versus 3 (range 0–6) in the ketoprofen group (p = 0.266). Median cramping scores 30 min post-procedure in the paracetamol group were 0 (range 0–5) vs. 0 (range 0–4) in the ketoprofen group, respectively (p = 0.499). Side effects occurred in 3 participants (10%) in the ketoprofen group and none of the paracetamol group. Comfort scores were high in both groups (median 9/10). No vagal reflexes were observed. Conclusions: Oral 1000 mg paracetamol was as effective as oral 100 mg ketoprofen for pain management during and after office hysteroscopy, with fewer side effects. Paracetamol may be a safe and cost-effective alternative for pre-procedure analgesia in office hysteroscopy. Full article

Wound dressing coverages (WDC) play a key role in protecting skin lesions and preventing infection. Polymeric membranes have been widely explored as WDC due to their ability to incorporate bioactive agents, including antimicrobial nanoparticles and non-steroidal anti-inflammatory drugs (NSAIDs). In this study, polycaprolactone (PCL)-based membranes functionalized with titanium dioxide nanoparticles (TiO₂ NPs) and ibuprofen (IBP) were fabricated using a film manufacturing approach, and their structural and biocompatibility profiles were evaluated. The membranes were characterized by SEM, FTIR and XPS. Bands at 1725 cm⁻¹, 2950 cm⁻¹, 2955 cm⁻¹, 2865 cm⁻¹ and 510 cm⁻¹ proved molecular stability of reagents during manufacture. In SEM, the control shows the flattest surface, while the PCL-IBP and PCL-IBP-TiO₂ NPs groups had increased rugosity. In vitro biocompatibility was evaluated using human fetal osteoblasts (hFOB). On day 3, the cell adhesion response of hFOB seeded in PCL-IBP and PCL-IBP-TiO₂ NPs groups showed the biggest absorbances (p = 0.0014 and p = 0.0491, respectively). On day 7 PCL-IBP group had lower lectin binding than the control (p = 0.007) and the PCL-IBP-TiO₂ NPs (p = 0.015) membranes, but no evidence of cytotoxicity was observed in any group. Furthermore, the Live/Dead test adds more biocompatibility evidence to conveniently discriminate between live and dead cells. The PCL polymeric membrane elaborated in this study may confer antiseptic, analgesic and anti-inflammatory properties, making these membranes ideal for skin lesions. Full article

Background: Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for clavicle fracture pain management carry significant adverse effect and allergic reaction risks. This study assessed ultrasound-guided nerve block (USNB) efficacy for acute clavicle fracture pain in emergency department (ED) patients, providing an alternative to NSAIDs and opioids with fewer adverse effects. Methods: This retrospective, single-center observational study was conducted in accordance with Methods of Medical Record Review Studies in Emergency Medicine Research guidelines. Adult patients (≥20 years) who presented to the ED with traumatic clavicle fractures between 1 January 2015 and 30 November 2023 were included. Of the 343 eligible patients, 12 received ultrasound-guided nerve blocks (USNB) and 331 received standard care. To improve exchangeability, 1:10 matching with replacement was performed according to patients’ characteristics, such as age, sex, initial pain score, and comorbidities. The primary outcome was pain relief, assessed via the pain intensity difference (PID) on the Numerical Rating Scale within 360 min post-intervention. Meaningful pain relief was defined as a PID ≥ 4. Secondary outcomes included rescue opioid use, ED length of stay, hospital length of stay, and USNB-associated complications, such as vascular puncture, nerve injury, or local anesthetic systemic toxicity. Data were analyzed using time-course, time-to-event (time to meaningful pain relief), and linear regression analyses. Results: A total of 12 patients in the USNB group and 85 matched patients in the standard care group were analyzed after baseline characteristics matching with replacement. Compared to standard care, USNB was associated with significantly greater pain relief (p < 0.001). In the time-to-event analysis, USNB led to a 3.41-fold faster achievement of meaningful pain relief compared with that achieved with standard care (HR = 3.41; 95% CI, 1.47–7.90; p = 0.004). No significant differences were observed between groups in rescue opioid use, ED length of stay, or hospital length of stay. No USNB-associated complication developed in the USNB group. Conclusions: In patients with traumatic clavicle fractures, USNB provides more rapid and sustained pain relief than standard analgesic care in the ED, without increasing the ED length of stay. Large prospective studies are needed to confirm these findings. Full article

The treatment of diabetes in the modern era, with its growing patient population, represents a significant challenge due to the wide range of adverse effects associated with medications that target complex biochemical processes. Consequently, researchers are investigating the hypoglycemic potential of existing drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, fever, and various inflammatory conditions. Recent studies have shown that NSAIDs, particularly salicylates, can influence glycemia through multiple mechanisms, including inhibition of gastrointestinal enzymes, blockade of K_ATP channels, activation of AMP-activated protein kinase (AMPK), and inhibition of NF-κB signaling, among others. Accordingly, this review explores the hypoglycemic potential of NSAIDs as well as their derivatives, and the diverse mechanisms through which these molecules may influence glucose homeostasis. Full article

Background/Objectives: Fever and pain are among the most common symptoms in pediatric infections and chronic diseases, causing significant discomfort for children and concern for caregivers. Effective management is essential to relieve distress while avoiding overtreatment or undertreatment. Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), particularly ibuprofen, are the primary antipyretic and analgesic agents in pediatric care, but their use in children with chronic conditions might be challenging. Methods: A narrative review and clinical expert judgment were used to synthesize current evidence on the use of paracetamol and NSAIDs (especially ibuprofen) in children with some common chronic diseases. Results: Paracetamol is often considered a first-line option in several chronic conditions. Caution is warranted in children with pre-existing malnutrition, obesity, and neuromuscular disorders as these factors might increase the risk of hepatotoxicity. NSAIDs provide additional anti-inflammatory effects and comparable analgesic efficacy but should be used cautiously in some high-risk populations due to potential gastrointestinal, renal, and bleeding complications. Their use is contraindicated in children with dehydration, renal impairment, nephrotic syndrome relapses, while careful risk-benefit assessment is required in small and vulnerable neonates. Some data also suggests NSAIDs may worsen outcomes in certain acute bacterial and viral infections. Data on chronic infections such as tuberculosis, HIV, and viral hepatitis are limited, highlighting the need for further research. Combination therapy with paracetamol and ibuprofen may enhance analgesia in postoperative settings without significantly increasing adverse events. Overall, available evidence is limited and largely observational. Conclusions: This narrative review synthesizes current evidence and clinical expertise to provide practical guidance on the rational use of paracetamol and NSAIDs in children, emphasizing individualized therapy according to comorbidities, risk factors, and clinical context, particularly in vulnerable populations. A risk-adapted, evidence-based approach ensures optimal symptom control while minimizing harm, supporting safer, more effective, and family-centered care for children with fever and pain. Full article

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain management but pose gastrointestinal (GI) and cardiovascular (CV) risks, particularly during long-term use. This study evaluated NSAID-prescribing patterns and the appropriateness of gastroprotective co-therapy among patients with varying GI and CV risk profiles. Methods: An observational, cross-sectional study was conducted in the outpatient pharmacy department over six months (March 2023 to August 2023) at a public secondary care facility. Data pertaining to patient demographics, NSAIDs prescription, and GI/CV risks were collected and reviewed from electronic health records. Descriptive statistics, chi-square tests, and logistic regression were performed. Results: A total of 1005 prescriptions containing 2051 NSAIDs were analyzed. Selective COX-2 inhibitors and non-selective NSAIDs were the most frequently prescribed. Only 42.1% of patients received proton-pump inhibitors despite guideline recommendations. Non-selective NSAIDs were significantly associated with CV history and GI risk (p < 0.0001). Logistic regression showed age, gender, CV history, and GI risk significantly influenced NSAID selection. Notably, non-selective NSAIDs continued to be prescribed among moderate- and high-GI-risk patients. Conclusions: Suboptimal adherence to guideline-recommended gastroprotective strategies was evident, particularly among high-risk patients. Comprehensive GI and CV risk assessment and the rational use of gastroprotective co-therapy are essential. Integrating evidence-based digital tools may enhance safer NSAID prescribing in routine practice. Full article

Diabetic foot ulcers (DFUs) represent 6.3% of the various complications of type 2 diabetes mellitus, with a risk of development of up to 34%. Several factors contribute to the formation of ulcers, which are very difficult to treat as they hinder efficient wound healing. Patients experience persistent pain, which leads to the consumption of various medications (polypharmacy) due to the lesions not resolving. Conversely, this can increase the risk of various factors, including a chronic inflammatory state, which hinders the body’s own regenerative processes. Until now, treatment options have been limited to washing the wound and stimulating new tissue growth, but this is a painful and unsuccessful process. One of the treatment options is therefore cell therapy with mesenchymal stem cells, which have immunomodulatory characteristics and allow tissue regeneration, although the effect directly in pain is not totally clear. We have previously reported in our working group that patients with ulcers treated with mesenchymal stem cells (MSCs) have been able to integrate into their daily lives, although the pain related to the inflammatory state and polypharmacy has not been studied. Objective: This study investigates how the local administration of MSCs improves the condition of an ulcer by inducing tissue regeneration. It also shows how the concentration of systemic inflammatory biomarkers is modified in direct correlation with pain and the consumption of medications over time. Methods: Local administration of MSCs at 7 and 14 days, measuring pro- and anti-inflammatory cytokines relative to the healthy control group, evaluating wound healing, and monitoring the medications taken by the patient in conjunction with pain perception. Results: Cell administration showed that inflammatory molecules were reduced and anti-inflammatory molecules increased. This is reflected in the consumption of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in relation to wound improvement, with a decrease in pain medication consumption of less than 50%. We provide evidence that locally administered mesenchymal stem cells influence systemic inflammatory processes necessary for tissue recovery, impacting patients’ polypharmacy consumption due to reduced perceived pain. Conclusions: This report establishes a direct link between mesenchymal stem cells and pain relief in type 2 diabetes ulcers, potentially paving the way for new pain therapies. Full article

Carboxyxanthones containing carboxylic acid groups linked to lipophilic aromatic rings resemble the key pharmacophoric features of many nonsteroidal anti-inflammatory drugs (NSAIDs). This structural similarity makes them attractive scaffolds for the development of new anti-inflammatory agents. This study describes the production, cytocompatibility, and anti-inflammatory potential of ten carboxyxanthones (1–10) and two intermediates (11–12) by evaluating their effects on key pro-inflammatory mediators, namely interleukin 6 (IL-6) and prostaglandin E2 (PGE₂). As these compounds are produced by distinct mechanisms, their multi-target potential will be evaluated. Carboxyxanthones were obtained by multi-step pathways using different synthetic approaches through classical benzophenone or diaryl ether intermediates synthesis followed by intramolecular acylation. To the best of our knowledge, the synthesis of carboxyxanthones 3 and 5 is described herein for the first time. All tested compounds were cytocompatible with lipopolysaccharide (LPS)-stimulated macrophages. The most notable carboxyxanthones were 3, 4, 7, and 8, which were able to significantly reduce IL-6 production by approximately 60%. Molecular docking simulations between compounds 1–12 and cyclooxygenase-2 were conducted to characterize the structural features underlying molecular recognition, and to identify the most promising candidates for subsequent PGE₂ assays. Carboxyxanthones 3, 5, and 6, as well as intermediate 12, were predicted to be the best. In the human in vitro inflammation model used, carboxyxanthone 6 exhibited the most potent and consistent inhibitory effect on PGE₂ production. At the highest concentration tested (100 µM), it presented an efficacy comparable to that of celecoxib. Carboxyxanthones 3 and 5 demonstrated a biphasic effect, decreasing and increasing PGE₂ production at lower (5, 12.5, and 25 µM) and higher (50 and 100 µM) concentrations, respectively. These results highlight the potential of carboxyxanthones as promising modulators of inflammatory pathways, paving the way for further studies aimed at elucidating their mechanisms of action, optimizing structural features, and assessing their safety and therapeutic potential in relevant disease models. Full article

Background: Gastrointestinal (GI) mucosal injury is a frequent complication of long-term nonsteroidal anti-inflammatory drug (NSAID) use. Effective mucosal healing requires coordinated epithelial migration, proliferation, and angiogenesis, which may be influenced by focal adhesion kinase (FAK). This study aimed to determine whether our newly developed FAK activators promote intestinal mucosal healing by enhancing angiogenesis and whether FAK activation increases resistance to reinjury. Methods: Ischemic jejunal ulcers were induced in C57BL/6 mice. After 24 h, mice received intraperitoneal injections of the FAK activator ZINC40099027 (ZN27, 900 µg/kg every 6 h) or vehicle for 2, 4, or 14 days. Ulcer areas were quantified, and liver and kidney function were assessed. Ulcer and adjacent tissues were analyzed by immunofluorescence staining for angiogenesis and proliferation markers. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with ZN27 to evaluate proliferation, migration, angiogenesis, and intracellular signaling. In a reinjury model, male C57BL/6J mice received continuous infusion of the FAK activator M64HCl (25 mg/kg/day) or vehicle for 7 days, with a single subcutaneous injection of indomethacin (10 mg/kg) on day 1 to induce GI injury. Fourteen days after the first dose of indomethacin, the mice received a second indomethacin challenge, and one day later, total ulcer areas in the pyloric opening and small intestine were quantified. Results: Ulcer areas were significantly smaller in ZN27-treated mice compared with vehicle-treated controls at 3 and 5 days, accompanied by increased expression of angiogenesis and proliferation markers. In vitro, ZN27 enhanced HUVEC migration via FAK activation in an ERK1/2-dependent manner and increased the number of angiogenic sprouts. In the reinjury model, treatment with M64HCl during the initial indomethacin-induced injury resulted in significantly smaller ulcer areas in both the pyloric opening and small intestine after the second indomethacin challenge compared with controls. Conclusions: FAK activation accelerates ischemic ulcer healing, in part by enhancing angiogenesis. Moreover, FAK activation during an initial injury reduces susceptibility to recurrent NSAID-induced intestinal injury, perhaps because it promotes initial higher-quality ulcer repair. Full article

Osteoarthritis (OA) is a common and debilitating degenerative joint disease associated with aging and more common among women. OA is a disease that affects many parts of the joint, including cartilage, subchondral bone, and the synovium. Although the exact cause of OA is still under investigation, major factors include dysregulation of inflammatory cytokines and loss of function of mesenchymal stem cells (MSCs). Unfortunately, current treatments for OA are limited to symptomatic management, including nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular injections such as hyaluronic acid (or cortisol), physical therapy, and surgical intervention, none of which can affect disease progression or provide permanent solutions. Currently there is no FDA approved treatment that can address the molecular basis of OA, although some promising candidates include bone marrow-derived MSC injection, adipose-derived MSC injection, pulsed electromagnetic field (PEMF), TissueGene-C, and CK2.1. Full article

Introduction: Toxic Epidermal Necrolysis (TEN) and Steven–Johnson Syndrome (SJS) are rare yet dangerous dermatological emergencies presenting as necrosis of the skin and mucous membranes due to an immune reaction which may be associated with the use of pharmaceuticals—predominantly non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, and antiretroviral drugs. During the postpartum period, women are administered numerous pharmaceuticals, including NSAIDs, analgesics, and antibiotics, due to pain and their susceptibility to infections, exposing them to potential adverse effects including allergies and immune reactions. Case Report and Review: The case reported here is a rare description of a patient in the early postpartum phase who presented with epidermal necrolysis whilst remaining hospitalized after a cesarean delivery. The multidisciplinary approach, early diagnosis, and treatment ensured the patient’s full recovery. Intravenous immunoglobulin treatment resulted in a rapid therapeutic effect. This literature review offers an insight into the epidemiology, diagnostic process, and treatment of this infrequent dermatological syndrome during the postpartum period. Results: Antibiotic treatment is a common culprit of TEN in this population; hence, clinicians should remain vigilant during antibiotic administration. Differential diagnosis with toxic shock syndrome is crucial, as TEN and SJS symptoms may mimic sepsis, which is a more common diagnosis in the postpartum period. Conclusions: The condition of the skin during the postpartum period should be closely monitored, as some systemic diseases may manifest abruptly as profound, postpartum hormonal changes affect the immunological response. Upon the discovery of suspicious skin lesions concomitant with systemic symptoms, an immediate multidisciplinary approach involving obstetricians and dermatologists is key to a rapid diagnosis and treatment to avoid maternal mortality. Full article

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality, with inflammation playing a pivotal role in its pathogenesis. Chronic inflammation in the intestine significantly increases the risk of CRC development. Main compounds participating in the inflammatory process are prostaglandins; bioactive lipids derived from arachidonic acid metabolism via the cyclooxygenase (COX) pathway. While it is well known that prostaglandin E₂ (PGE₂) promotes CRC tumorigenesis, other prostaglandins, such as PGD₂, PGF_2α, and prostacyclin (PGI₂), remain relatively underexplored. These prostaglandins may exert distinct or opposing effects on CRC development, but the current understanding of their functions is limited. Additionally, the impact of prostaglandins on immune regulation and the tumor microenvironment, is far from being fully understood. Addressing these knowledge gaps is crucial for identifying novel therapeutic targets and optimizing chemoprevention strategies. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of CRC, largely by inhibiting prostaglandin producing enzymes. However, their use is limited due to their gastrointestinal and cardiovascular side effects. Therefore, understanding the intricate role of inflammation and prostaglandin signaling in CRC is critical to develop safer and more effective chemopreventive approaches. This review summarizes the current knowledge of prostaglandins, linking inflammation and CRC. It further addresses the potential of targeting prostaglandin pathways for chemoprevention. Furthermore, we discuss emerging pharmacological targets that modulate prostaglandin production, signaling or degradation, offering promise for preventing CRC development. Full article

Background/Objectives: Acute low back pain (LBP) is a prevalent cause of disability worldwide. If often involves both inflammation and reflex muscle spasm, suggesting combined therapy with a non-steroidal anti-inflammatory drug (NSAID) and a muscle relaxant may provide superior relief. This study aimed to evaluate the short-term efficacy and safety of a single intramuscular (IM) injection of a fixed-dose combination (FDC) product containing Diclofenac and Thiocolchicoside versus Diclofenac monotherapy in adults with acute LBP. Methods: We conducted a phase III multicenter, randomized, double-blind, parallel-group trial in 140 patients with acute LBP of moderate to severe intensity. Patients were allocated 1:1 to receive either the combination of Diclofenac sodium 75 mg + Thiocolchicoside 4 mg (FDC product, Test Group) or Diclofenac sodium 75 mg alone (Diclofenac monotherapy, Reference Group) via a single IM injection. The primary outcome was the change in patient-reported pain intensity using the Visual Analogue Scale (VAS) from baseline to 3 h post-dose. Key secondary outcomes included pain change at 1 h in the VAS, improvement in lumbar mobility (finger-to-floor distance test, FTF), the proportion of patients achieving >30% pain reduction, and the incidence of adverse events (AEs). Randomization was centralized and both investigators and patients were blinded to the treatment. Results: All 140 randomized patients completed the trial. At 3 h post-injection, the combination therapy produced a significantly greater mean pain reduction than monotherapy (41.52 mm vs. 28.13 mm on the 100 mm VAS; p < 0.0001). Superiority of the combination was already evident at 1 h post-dose (VAS reduction 27.61 mm vs. 20.40 mm; p = 0.0089). Lumbar flexion improved more with the combination at 3 h (mean FTF distance improvement 14.52 cm vs. 7.94 cm; p < 0.0001) and at 1 h (9.21 cm vs. 4.62 cm; p < 0.0001). A higher proportion of patients achieved >30% pain relief with the combination (45.7% vs. 27.2% at 3 h, p < 0.0001; 31.4% vs. 18.6% at 1 h, p = 0.0066). Only one mild, transient adverse event (headache) was reported in the combination group (1.4% of patients) and none in the diclofenac-only group. No serious AEs occurred. Conclusions: A single intramuscular dose of diclofenac plus thiocolchicoside provided faster, greater relief of acute LBP than diclofenac alone, without compromising safety. The combination therapy significantly reduced pain and muscle spasm-related mobility limitations within 1–3 h and was well tolerated. These results support the combined use of an NSAID and muscle relaxant as an effective and safe option for acute moderate-to-severe LBP management. Full article

The aim of this study was to investigate the molecular interactions of heparin, diclofenac, and their supramolecular complexes with cyclooxygenase enzymes (COX-1 and COX-2) using computational docking techniques. Diclofenac is a widely used nonsteroidal anti-inflammatory drug (NSAID) that inhibits COX isoforms, whereas heparin is a polyanionic glycosaminoglycan with established anticoagulant and emerging anti-inflammatory properties. Supramolecular association between these agents may modulate their physicochemical behavior and target engagement. Molecular modeling, dual-drug docking, and molecular dynamics (MD) simulations were employed to characterize the interactions of heparin, diclofenac, and pre-formed heparin–diclofenac complexes with COX-1 and COX-2. Geometry optimization and lipophilicity (logP) estimates were obtained using HyperChem, while protein–ligand docking was performed in HEX using crystallographic COX structures from the Protein Data Bank. Docking poses were analyzed in Chimera, and selected complexes were refined through short MD simulations. Pre-formed heparin–diclofenac assemblies exhibited markedly enhanced docking scores toward both COX isoforms compared with single ligands. Binding orientation strongly influenced affinity: for COX-1, the heparin–diclofenac configuration yielded the most favorable interaction, whereas for COX-2 the diclofenac–heparin configuration was preferred. Both assemblies adopted binding modes distinct from free diclofenac, suggesting cooperative electrostatic and hydrophobic contacts at the enzyme surface. Supramolecular complexation also altered calculated logP values relative to the individual compounds. MD simulations supported the relative stability of the top-ranked complex–COX assemblies. These findings indicate that heparin–diclofenac assemblies may enhance and reorganize predicted COX interactions in a configuration-dependent manner and illustrate the utility of dual-drug docking for modeling potential synergistic effects. Such insights may inform the design of localized or topical formulations, potentially incorporating non-anticoagulant heparin derivatives, to achieve effective COX inhibition with reduced systemic exposure. However, the results rely on simplified heparin fragments, legacy docking tools, and short MD simulations, and should therefore be interpreted qualitatively. Experimental studies will be essential to confirm whether such supramolecular assemblies form under physiological conditions and whether they influence COX inhibition in vivo. Full article