Selective Cyclooxygenase-2 Inhibitor Research Articles

COX-2/PGE2/VEGF signaling promotes ERK-mediated BMSCs osteogenic differentiation under hypoxia by the paracrine action of ECs.

Understanding the crosstalk between endothelial cells (ECs) and bone-marrow mesenchymal stem cells (BMSCs) in response to hypoxic environments and deciphering of the underlying mechanisms are of great relevance for better application of BMSCs in tissue engineering. Here, we demonstrated that hypoxia promoted BMSCs proliferation, colony formation, osteogenic markers expression, mineralization, and extracellular signal-regulated protein kinase (ERK) phosphorylation, and that PD98059 (ERK inhibitor) blocked hypoxia-induced osteogenic differentiation. Hypoxia enhanced ECs migration, cyclooxygenase 2 (COX-2) and integrin αvβ3 expression, and prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF) secretion. NS398 (selective COX-2 inhibitor) and LM609 (integrin αvβ3 specific inhibitor) impaired the ECs response to hypoxia, and exogenous PGE2 partially reversed the effects of NS398. BMSCs: ECs co-culture under hypoxia upregulated BMSCs osteogenesis and ERK phosphorylation, as well as ECs migration, integrin αvβ3 expression, and PGE2 and VEGF secretion. NS398 (pretreated ECs) lessened PGE2, VEGF concentrations of the co-culture system. NS398-treated ECs and AH6809 (combined EP1/2 antagonist)/L-798106 (selective EP3 antagonist)/L-161982 (selective EP4 antagonist)/SU5416 [VEGF receptor (VEGFR) inhibitor]-treated BMSCs impaired the co-cultured ECs-induced enhancement of BMSCs osteogenic differentiation. In conclusion, hypoxia enhances BMSCs proliferation and ERK-mediated osteogenic differentiation, and augments the COX-2-dependent PGE2 and VEGF release, integrin αvβ3 expression, and migration of ECs. COX-2/PGE2/VEGF signaling is involved in intercellular BMSCs: ECs communication under hypoxia.

Anti-inflammatory activity of novel natural plant extracts composition—LevidorTM

Abstract Introduction Due to the severe side effects of non-steroidal anti-inflammatory drugs, there is an urgent need to find new natural or synthetic chemicals that could act as selective inhibitors of cyclooxygenase-2 (COX-2). The most valuable source of new bioactive compounds and potential drugs are plants. The present study aimed at the investigation of LevidorTM, a patented composition based on oil from the seeds of Nigella sativa and extract from the root of Angelica archangelica, regarding its potential anti-inflammatory effects on the molecular level. Materials and Methods Studies were carried out with the use of murine macrophages (RAW 264.7), human monocytes (U937), and rat pheochromocytoma (PC-12) cell lines. The cytotoxicity of the LevidorTM extract was evaluated by MTT assay. The concentration of pro-inflammatory cytokines (IL-6, TNF-α) was evaluated by ELISA. Moreover, the analysis of COX-1 and COX-2 mRNA expression levels by RT-PCR, as well as protein level by Western blot and immunofluorescent staining, were assessed. Results The LevidorTM extract did not impact cell growth and showed anti-inflammatory effect in the present study. It was able to decrease the level of IL-6, TNF-α and suppress transcription of COX-2, whereas it had no effect on COX-1. Conclusions Obtained results showed that LevidorTM exhibits strong anti-inflammatory properties and may provide a significant alternative to traditionally used medicines in acute pain and chronic inflammation.

Usage of COX-1 and COX-2 Nanomedicines in Nanotechnology

Nanomedicine is the branch of medical applications in nanotechnology. Nanomedicine ranges from medical applications of nanomaterials, biological devices to nanoelectronic biosensors, molecular nanotechnology such as biological machines. It utilizes knowledge and tools of nanotechnology to prevention and treatment of disease. Nanomedicine involves use of nanoscale materials such as biocompatible nanoparticles for delivery, sensing or actuation in a living organism. COX inhibitors are a class of pharmaceutical compounds that selectively target and inhibit the activity of the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). These enzymes are key players in the synthesis of prostaglandins, which are important mediators of inflammation, pain, and fever in the body. By modulating prostaglandin production, COX inhibitors have significant therapeutic implications in the management of various inflammatory conditions, pain relief, and fever reduction. COX-1 is constitutively expressed in many tissues and is involved in maintaining normal physiological functions, including the protection of the stomach lining and platelet aggregation. In contrast, COX-2 is induced at sites of inflammation and is primarily responsible for producing prostaglandins involved in the inflammatory response. The selective inhibition of COX-2 allows for targeted suppression of inflammation while preserving the beneficial functions of COX-1. Moreover, recent research has shed light on the complex interplay between COX-1 and COX-2 in health and disease. Emerging evidence suggests that the balance between COX-1 and COX-2 inhibition may have implications beyond pain and inflammation. Investigating the diverse roles of these enzymes in different tissues and pathologies may open up new avenues for drug development and personalized medicine. COX inhibitors represent an important therapeutic class with a profound impact on managing pain, inflammation, and related disorders. Understanding the differential regulation and functions of COX-1 and COX-2 is crucial for optimizing the clinical use of COX inhibitors and developing novel strategies for targeted and safer anti-inflammatory therapies.

An update on clinical trials for chemoprevention of human skin cancer.

The pathophysiology of skin cancer is complex, with multiple factors contributing to its development. The proactive treatment of skin cancer has been investigated in the form of chemoprevention of cutaneous malignancies in clinical trials. Chemoprevention is the use of natural or pharmacologic agents that prevent or reverse skin cancer development. Multiple trials have arisen over the past decades to explore the efficacy of specific agents to halt the progression of UV radiation damage. This comprehensive review article aims to assess clinical trials performed with chemopreventive agents for melanoma and nonmelanoma skin cancers. The following compounds were most often used in these trials: nicotinamide, retinoids, polyphenolic antioxidants, COX-2 selective inhibitors, non-steroidal anti-inflammatory drugs, difluoromethylornithine, and 5-fluorouracil. Many agents show promise in their ability to prevent nonmelanoma skin cancer formation, with few melanoma trials demonstrating efficacy. The chemoprevention efforts aimed at skin cancer are complex; current and future trials will be instrumental in identifying therapeutic agents that pose efficacy in halting cancer development and assessing whether long-term administration is tolerable.

Cu(II) and Fe(III) Catalyzed Synthesis of Novel Thiophene Hybridized Thiadiazolyl Schiff Bases (TTS) as COX-2 Selective Inhibitor

A novel series of thiophene hybridized thiadiazolyl Schiff bases (TTS) were designed and synthesized using copper nitrate (CuII) catalyzed synthesis of Schiff bases and their subsequent ferric chloride (FeIII) catalyzed cyclization into thiadiazoles. The design of molecules was inspired by the well-documented anti-inflammatory properties of thiadiazoles, Schiff bases and thiophene. Based on information from mass spectroscopy, IR, 1H and 13C NMR measurements, the structures of the recently synthesized compounds were determined. The purpose of molecular docking was to better understand the interactions between drug candidates and COX-1 (PDB ID: 3KK6) and COX-2 (PDB ID: 3Q7D) inflammation-related targets. Compounds 3a-f showed a more stable binding complex with COX-2 (-8.09 to -9.13 kcal/mol) when compared to COX-1 (-4.86 to -5.94 kcal/mol). Additionally, the carrageenan-induced rat paw oedema model was used for the in vivo analysis and compound 3a demonstrated excellent anti-inflammatory activity when compared to the reference drug, diclofenac. Interestingly, the mRNA expression analysis using qRT-PCR demonstrates a specific suppression of COX-2 as compared to COX-1, further supporting the earlier findings. Altogether, the findings could provide an opportunity for these compounds to be developed as novel lead molecules for rational alternatives of NSAIDS.

Nicht-steroidale Antirheumatika und kardiovaskuläres Risiko

Non-steroidal Anti-inflammatory Drugs and Cardiovascular Risk Abstract. Non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most frequently used drugs worldwide, although medically controlled prescription is missing most of the time. Beside well-known gastro-intestinal and renal side effects, the potentially increased cardiovascular risk under NSAIDs remains underestimated. Nonselective NSAIDs, but also selective COX-2 inhibitors may block and decrease prostacyclin, which itself physiologically would inhibit platelets and promote vasodilation. Furthermore, in selective COX-2 inhibitors a shift towards COX-1 activity may be observed, which further promotes platelet aggregation. Nonselective NSAIDs with a long half-life time are characterized by relatively stable plasma levels and thus a relatively stable platelet inhibition. Non-selective NSAIDs may additionally inhibit acetylsalicylic acid, which negatively affects its effect on platelet inhibition.

Low-dose prophylaxis protocol for heterotopic ossification after hip preservation surgery in a sport participants cohort.

Heterotopic ossification (HO) is a well-known complication of arthroscopic and open surgical treatment of femoroacetabular impingement (FAI). Incidence of heterotopic ossification has been reported in the literature between 0% and 44% after hip arthroscopy and between 18.2% and 25% after anterior mini-open surgery. Currently, pharmacological prophylaxis with NSAIDs and selective COX-2 inhibitors are commonly used and their effectiveness is well documented in literature. We hypothesized that the low-dose prophylaxis protocol with selective cox-2 inhibitors decreases the risk of heterotopic ossification in open or arthroscopic hip preservation surgery in athletes. This study is an analysis of prospectively gathered data on 98 sport participant patients who underwent arthroscopic or anterior mini-open treatment for FAI between April 2008 and April 2018. All the patients received postoperative oral prophylaxis with 60mg etoricoxib once daily for two weeks. Post-operative X-rays were performed at 1, 3, and 12 months after surgery and reviewed by two orthopedic surgeons blinded to the type and side of surgery. HO were graded according to the Brooker classification. Descriptive statistics was used to analyze demographic data. Bivariate analysis was performed to analyze the association of HO with each of the following variables: type of surgery, physical activity, time of evolution of symptoms, age at surgery, and sex. Finally, a regression model analysis was performed to determine the presence of confounding effects between variables. The study cohort was composed of 54 patients in the arthroscopic treatment group and 44 patients in the anterior mini-open group. HO was identified in 6 (13.6%) patients in the mini-open group. No HO was identified in the arthroscopic group. In the bivariate analysis, "type of surgery" was the only variable that showed a statistically significant association with HO (p=0.007). Results of this study suggest that anterior mini-open treatment was characterized by a higher risk of HO development compared to hip arthroscopy for femoroacetabular impingement treatment regardless of pharmacological prophylaxis. The treatment regimen of 60 mg etoricoxib daily for two weeks was an effective prophylaxis for HO formation in sport participant patients compared with data available in the literature.

Anticonvulsant property of celecoxib in maximal electroshock seizure: Correlating the role of inflammation in pathophysiology of epileptic seizures

Background: Epilepsy is an abnormal excessive electric neuronal activity and always represents by recurrent seizures. There is positive feedback cycle between epileptogenesis and brain inflammation. It has been proved that an inflammatory enzyme, cyclooxygenase (COX) (especially isoform-2, a constitutive enzyme), expressed in some important parts of the central nervous system and is responsible to induced inflammation locally and having seizurogenic property. Aim and Objective: The goal of this study was to see if celecoxib (a selective COX-2 inhibitor) could reduce the maximal electroshock seizure (MES)-induced seizures in mice. Materials and Methods: Celecoxib injected intraperitoneally in two different doses 5 mg/kgb/w and 10 mg/kg b/w, in albino Swiss mice and in two different phases. MES was elicited and length of different phases was noted. Length of tonic hindlimb extension was considered as indicator of anti-epileptic activity. Results: Celecoxib, when given intraperitoneally, exert significant reduction in the duration of THLE. This action of celecoxib strongly suggests the involvement of inflammation in the pathophysiology of epilepsy. Conclusion: The findings are suggestive of the therapeutic significance of celecoxib, as a future antiepileptic agent for seizure management.

Design, synthesis, molecular docking and molecular dynamic studies of novel benzimidazole–thiazole derivatives as potent and selective COX-2 inhibitors

New benzimidazole–thiazole compounds were synthesized to selectively inhibit COX-2.

Efficacy of Celecoxib and Diclofenac Sodium in the Management of Postoperative Pain, Swelling and Mouth Opening after Surgical Removal of Impacted Third Molars: A Split-mouth Randomised Clinical Study

Introduction: The surgical removal of mandibular third molars is generally followed by complaints of pain, trismus, and swelling. The duration of surgery and the reflection of a mucoperiosteal flap have been shown to affect the intensity and frequency of postoperative complaints. Pain from third molar surgery typically begins within one to three hours after surgery and ranges in intensity from moderate to severe. Numerous analgesics have been used to minimise pain and discomfort following the surgical removal of impacted third molars. Commonly used agents include ibuprofen, diclofenac sodium, paracetamol, or their combinations. Newer drugs, such as selective COX inhibitors, have not been extensively used for minor oral surgical procedures. Aim: To compare the clinical efficacy of celecoxib and diclofenac sodium on pain, swelling, and mouth opening after the surgical removal of impacted mandibular third molars. Materials and Methods: A split-mouth randomised controlled clinical trial was conducted in the Department of Oral and Maxillofacial Surgery at BharatiVidyapeeth DU Dental College and Hospital, Pune, Maharashtra, India. The study duration was six months, from August 2022 to January 2023. A total of 21 subjects (11 males and 10 females) who required surgical extraction of an impacted mandibular third molar were selected. All subjects were randomly allocated to receive one of the following treatments twice a day for five days after surgery: celecoxib 200 mg (n=11) or diclofenac sodium 75 mg (n=10). Pain scores were evaluated using the Visual Analogue Scale (VAS) on postoperative day one, two, and three. Swelling and mouth opening were evaluated on Postoperative Day (POD) two and seven. Intergroup comparison was done using Student’s t-test. Results: The mean age of the study participants was 28±1.5 years, and the mean VAS score for pain evaluation with celecoxib was 6.61, 5.38, and 5.00 on day 1 (p=0.027), 2 (p=0.972), and 3 (p=0.809), respectively. The difference in swelling values for the celecoxib group was significant, while there were no significant differences in the values of mouth opening. Conclusion: It was concluded that celecoxib 200 mg is a better analgesic and anti-inflammatory compared to diclofenac sodium 75 mg. Celecoxib was easily tolerable and comfortable for the patients. There was no significant difference in the values of mouth opening.

Discriminative Disintegration Techniques For Various Brands of NimesulideTablets Available in the Market

Background Nimesulide is a non-steroidal anti-inflammatory selective inhibitor of the enzyme cyclooxygenase with analgesic and antipyretic properties. It is approved to treat acute pain symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years age.Objective This article describes the recent research on the bioequivalence of six brands of Nimesulide tablets. Due to the large variety of Nimesulide tablet brands accessible in the Indian market medical practitioners face a tough challenge of selecting the best brand or using alternative treatments. The study presented assessed all six tablet brands in accordance with Indian Pharmacopoeia IP guidelines and the appropriate methods were provided for choosing the best options.Methodology All six tablet brands were evaluated utilizing in vitro tests using various evaluation techniques. Six different brands of tablets were used in the in vitro dissolving experiment and all of the tablets cleared the standards for general quality evaluation tests such as hardness friability disintegration time and dissolve time. All of the tested brands met the requirements for the disintegration time. With the exception of brand names Nimek and Bigesic every brand released more than 45 of the Nimesulide after 30 min. Auronim Novogesic Zega and Nise have a very sluggish rate of dissolution which indicates that their bioavailability is most likely to be low. The variations in the reported dissolving profiles could be due to differences between the manufacturers in terms of formulation ingredients the physical form of medicine used in the tablet and the manufacturing method.Results The result emphasizes the importance of continuous monitoring of new Nimesulide brands introduced to the drug market to ensure bioequivalence and compliance with pharmacopoeia standards.Conclusion The results conclude that with the exception of Nimek and Biogesic all of the Nimesulide tablet brands investigated appear to have a high dissolution rate with extremely good bioavailability releasing gt45 percent Nimesulide within 30 minutes and thus satisfied the Indian Pharmacopoeia criterion for uncoated tablet dissolution. Auronim Zega Nise and Novogesic are interchangeable and bioequivalent.

Doking studije nekih jedinjenja sa pirazolom u aktivnom mestu ciklooksigenaze-2

Whereas nonselective nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen and diclofenac, inhibit both cyclooxygenase-1 and cyclooxigenase-2 enzymes, selective inhibitors target cyclooxygenase-2, which is overexpressed in inflammation, but also in cancer, atherosclerosis, Alzheimer's disease, and Parkinson's disease. Potential cardiovascular and hepatic side effects of cyclooxygenase-2 inhibitors have limited their use. The development of selective and safe cyclooxygenase-2 inhibitors remains a high priority in drug discovery. Based on the structure of previously investigated newly synthesized b-hydroxy-b-arylpropanoic acids, two groups of compounds were designed: analogs in which one of the benzene rings was replaced by a pyrazole, while the carboxyl group was retained, and amides of b-hydroxy-b-arylpropanoic acids with pyrazole. The compounds were docked into the 3D structure of the catalytic site of the enzyme cyclooxygenase-2 using AutoDock Vina 1.2.0. and the obtained interactions were compared with the interactions of celecoxib, a selective inhibitor. The amides had lower binding energies than the designed acids, which makes them attractive target compounds for synthesis and further examination.

Bioassay Guided Isolation of Anti-Inflammatory Compounds from Bauhinia variegata L.: A Key Ingredient in Herbo-Mineral Formulation, Gandmala Kandan Ras

Medicinal herb Bauhinia variegata L. is the main ingredient in “Gandmala Kandan Ras” herbomineral medicine used in Ayurveda for the treatment of swelling, inflammation and tumors. This study aimed to isolate the anti-inflammatory compounds from the methanolic extract of aerial parts of Bauhinia variegata. Through bioassay-guided isolation, three known flavonoids, namely kaempferol, ombuin and quercetin were identified from methanolic extract of aerial parts of Bauhinia variega. The primary screening by protein denaturation method revealed a significant percentage of inhibition of protein denaturation of compounds kaempferol and quercetin. The anti-inflammatory assays against COX-1/2 enzymes showed significant anti-inflammatory activity of these two compounds, compared to the standard drug, indomethacin. Of which, quercetin as a potent non-selective inhibitor of COX1 and COX2 with minimal inhibitory concentration values of 172.05±4.29 and 220.62±9.13 nM, respectively; while kaempferol showed selective COX2 inhibition with the IC50 of 154.86±5.60 nM. The results provided evidence that supports the Ayurvedic usage of Gandmala Kandan Ras formulation in the treatment of inflammation, which was attributed to the natural active kaempferol and quercetin. The results indicated that plant Bauhinia variegata could be considered as an excellent natural source of remedial medicine for inflammation.

Different Medicinal Treatment Modalities in the Management of Patent Ductus Arteriosus in Paediatric Population- A Narrative Review of Available Drug Approaches

Regardless of the size of a patient’s Patent Ductus Arteriosus (PDA), it is crucial for paediatric and adult cardiologists to have a thorough understanding of the condition’s origin, clinical ramifications, and treatment options. Possessing a PDA, no matter how little, might cause complications. Ibuprofen and indomethacin, both cyclo-oxygenase (COX) inhibitors, are used as the gold standard pharmacologic therapy for closing a PDA that has been produced surgically. These non selective COX inhibitors bring about ductal constriction, in addition to lowering the synthesis of prostaglandin. However, these drugs may also have a broad array of unintended consequences. Interest in paracetamol for PDA constriction has recently increased due to fewer adverse effects than indomethacin or ibuprofen. Evidence that paracetamol is now a topic of intense study lends credence to this hypothesis. Information on the long term effects of paracetamol is scarce in paediatric population.

Comparative analysis of the effect of diclofenac sodium and etoricoxib on energy metabolism in rat liver in the acute general cooling model

When the ambient temperature decreases, physiological mechanisms that prevent heat loss are activated. However, under cold stress hypothermia develops, which significantly disrupts the functioning of the body and can be transformed into life-threatening. Preventive use of nonsteroidal anti-inflammatory drugs, especially diclofenac sodium and etoricoxib, has been found to reduce the severity of cold trauma. Given that their frigoprotective effect can accompany the impact on the synthesis of eicosanoids when exposed to low temperatures, it is advisable to study mechanisms for preventing hypothermia independent of cyclooxygenase, particularly the influence on energy metabolism. The aim of the study was to figure out the effect of diclofenac sodium and etoricoxib on the indicators of energy metabolism in the liver of rats after acute general cooling. Experiments were carried out on 28 sexually mature male rats, which were given diclofenac sodium (7 mg/kg), etoricoxib (5 mg/kg), or solvent 30 minutes before cold trauma intragastrically (in the intact control and pathology control groups). Acute hypothermia was caused by exposure of animals for 2 hours at a temperature of -18°C. Rectal temperature was measured before and after acute general cooling. The content of lactate, pyruvate and adenosine triphosphate in the liver was measured and the lactate/pyruvate ratio was calculated. Diclofenac sodium, unlike etoricoxib, was found to significantly reduce the severity of hypothermia. Both nonsteroidal anti-inflammatory drugs prevent energy metabolism disorders caused by exposure to cold, namely, reducing the concentration of lactic acid and the ratio of lactate/pyruvate, increasing the content of pyruvate and adenosine triphosphate in the liver of animals. Etoricoxib normalizes the content of energy metabolism intermediates to their levels in intact animals. Diclofenac sodium has a similar effect, the expression of which is inferior to the selective cyclooxygenase-2 inhibitor. Therefore, when administered prophylactically before acute general cooling, diclofenac sodium effectively prevents hypothermia in rats, surpassing etoricoxib. Etoricoxib completely prevents a decrease in the content of pyruvate and adenosine triphosphate, as well as the accumulation of lactic acid in the liver. Diclofenac sodium is inferior to etoricoxib in its effect on energy metabolism, which indicates other mechanisms of frigoprotective action of a non-selective cyclooxygenase inhibitor. The frigoprotective and energotropic properties of nonsteroidal anti-inflammatory drugs dissociate.

Celecoxib promotes the efficacy of STING-targeted therapy by increasing antitumor CD8+ T-cell functions via modulating glucose metabolism of CD11b+ Ly6G+ cells.

Recent studies have shown that activation of the cGAS-STING pathway is a key process in antitumor immune responses and various kinds of STING agonists have been developed for cancer immunotherapy. Despite promising preclinical studies, preliminary clinical results have shown only a modest effect of STING agonists. There is therefore a need to develop more effective treatment strategies. Based on previous observations that COX-2 is frequently overexpressed not only in a variety of cancers but also in tumor myeloid cells and that it suppresses antitumor immunity and promotes tumor survival by producing PGE2, we investigated the antitumor effects of combination therapy with a STING agonist cGAMP and the selective COX-2 inhibitor celecoxib in mouse models. Combination treatment with cGAMP and celecoxib inhibited tumor growth compared with either monotherapy, and the combination therapy induced both local and systemic antitumor immunity. cGAMP treatment decreased PD-1 expression on tumor-infiltrating T-cells and enhanced T-cell activation in tumor-draining lymph nodes regardless of the presence of celecoxib. Meanwhile, although celecoxib treatment did not alter the frequency of CD4+ CD25+ Foxp3+ regulatory T-cells, it enhanced the expression of costimulatory molecules and glycolysis-associated genes in tumor-infiltrating CD11b+ Ly6G+ cells. Moreover, we also found that celecoxib decreased lactate efflux and increased the frequency of IFN-γ- and TNF-α-producing CD8+ T-cells in the tumor microenvironment. Taken together, our findings suggest that combined treatment with celecoxib may be an effective strategy to improve the antitumor efficacy of STING agonists.

Transethosomal Gel for the Topical Delivery of Celecoxib: Formulation and Estimation of Skin Cancer Progression.

The topical delivery of therapeutics is a promising strategy for managing skin conditions. Cyclooxygenase-2 (COX-2) inhibitors showed a possible target for chemoprevention and cancer management. Celecoxib (CXB) is a selective COX-2 inhibitor that impedes cell growth and generates apoptosis in different cell tumors. Herein, an investigation proceeded to explore the usefulness of nano lipid vesicles (transethosomes) (TES) of CXB to permit penetration of considerable quantities of the drug for curing skin cancer. The prepared nanovesicles were distinguished for drug encapsulation efficiency, vesicle size, PDI, surface charge, and morphology. In addition, FT-IR and DSC analyses were also conducted to examine the influence of vesicle components. The optimized formulation was dispersed in various hydrogel bases. Furthermore, in vitro CXB release and ex vivo permeability studies were evaluated. A cytotoxicity study proceeded using A431 and BJ1 cell lines. The expression alteration of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and DNA damage and fragmentation using qRT-PCR and comet assays were also investigated. Optimized CXB-TES formulation was spherically shaped and displayed a vesicle size of 75.9 ± 11.4 nm, a surface charge of -44.7 ± 1.52 mV, and an entrapment efficiency of 88.8 ± 7.2%. The formulated TES-based hydrogel displayed a sustained in vitro CXB release pattern for 24 h with an enhanced flux and permeation across rat skin compared with the control (free drug-loaded hydrogel). Interestingly, CXB-TES hydrogel has a lower cytotoxic effect on normal skin cells compared with TES suspension and CXB powder. Moreover, the level of expression of the CDKN2A gene was significantly (p ≤ 0.01, ANOVA/Tukey) decreased in skin tumor cell lines compared with normal skin cell lines, indicating that TES are the suitable carrier for topical delivery of CXB to the cancer cells suppressing their progression. In addition, apoptosis demonstrated by comet and DNA fragmentation assays was evident in skin cancer cells exposed to CXB-loaded TES hydrogel formulation. In conclusion, our results illustrate that CXB-TES-loaded hydrogel could be considered a promising carrier and effective chemotherapeutic agent for the management of skin carcinoma.

Comparative Evaluation of the Effectiveness of the Treatment of Acute Pain Syndrome with a Selective COX1 and COX2 Inhibitor - Celecoxib without and against the Background of the Addition of a Combined Vitamin Complex of Group “B” In Patients with Nonspecific Pain Syndrome in the Lower Back

Comparative Evaluation of the Effectiveness of the Treatment of Acute Pain Syndrome with a Selective COX1 and COX2 Inhibitor - Celecoxib without and against the Background of the Addition of a Combined Vitamin Complex of Group “B” In Patients with Nonspecific Pain Syndrome in the Lower Back

Which non-steroidal anti-inflammatory drug (NSAID) is safer in patients with Non-steroids Exacerbated Respiratory Disease (N-ERD)? A single-center retrospective study.

In patients with NSAID-Exacerbated Respiratory Disease (N-ERD), respiratory symptoms occur as a result of the use of cyclooxygenase (COX)-1 inhibitor non-steroidal anti-inflammatory drugs (NSAIDs). Patients with N-ERD generally tolerate selective COX-2 inhibitor NSAIDs. However, respiratory symptoms may be exacerbated in patients with N-ERD due to the intake of selective COX-2 inhibitor NSAIDs. The aim of this study was to evaluate which selective or partial COX-2 inhibitor NSAID is safer in patients with N-ERD. Forty-nine patients with a history of respiratory hypersensitivity reactions to NSAIDs (N-ERD) who underwent a drug challenge test with celecoxib, nimesulide, meloxicam, and paracetamol between January 2021-April 2022 were retrospectively evaluated. Of the 49 patients who underwent the drug challenge tests, 16 (32.7%) were male and 33 (67.3%) were female and the mean age was 37.67 ± 11.62 years. The most common comorbidities were chronic urticaria [n= 21 (42.9%)] and allergic rhinitis [n= 21 (42.9%)]. As a result of drug challenge tests, celecoxib, nimesulide, meloxicam, and paracetamol drug challenge tests were positive in 2 (4.1%), 8 (16.3%), 7 (14.3%) and 11 (22.4) patients, respectively. The rate of allergic reaction to celecoxib was statistically significantly lower than other drugs (p= 0.001). In paired comparisons of the drugs, the allergic reaction rate with celecoxib was statistically significantly lower than with nimesulide (p= 0.031) and paracetamol (p= 0.004). Selective COX-2 inhibitor NSAIDs are safe in patients with N-ERD. NSAIDs should be prescribed to these patients following general medical precautions and drug challenge tests.

Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients

Drug delivery platforms that allow for gradual drug release after intra-articular administration have become of much interest as a treatment strategy for osteoarthritis (OA). The aim of this study was to investigate the safety and efficacy of an intra-articular sustained release formulation containing celecoxib (CXB), a cyclooxygenase-2 (COX-2) selective inhibitor. Amino acid-based polyesteramide microspheres (PEAMs), a biodegradable and non-toxic platform, were loaded with CXB and employed in two in vivo models of arthritis: an acute inflammatory arthritis model in rats (n=12), and a randomized controlled study in chronic OA dog patients (n=30). In parallel, the bioactivity of sustained release of CXB was evaluated in monolayer cultures of primary dog chondrocytes under inflammatory conditions. Sustained release of CXB did not alleviate acute arthritis signs in the rat arthritis model, based on pain measurements and synovitis severity. However, in OA dog patients, sustained release of CXB improved limb function as objective parameter of pain and quality of life based on gait analysis and owner questionnaires. It also decreased pain medication dependency over a 2-month period and caused no adverse effects. Prostaglandin E2 levels, a marker for inflammation, were lower in the synovial fluid of CXB-treated dog OA patients and in CXB-treated cultured dog chondrocytes. These results show that local sustained release of CXB is less suitable to treat acute inflammation in arthritic joints, while safe and effective in treating pain in chronic OA in dogs.