scholarly journals Recent Findings on Thymoquinone and its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 775
Author(s):  
Ravi Raj Pal ◽  
Vasundhara Rajpal ◽  
Priya Singh ◽  
Shubhini A. Saraf

Cancer causes a considerable amount of mortality in the world, while arthritis is an immunological dysregulation with multifactorial pathogenesis including genetic and environmental defects. Both conditions have inflammation as a part of their pathogenesis. Resistance to anticancer and disease-modifying antirheumatic drugs (DMARDs) happens frequently through the generation of energy-dependent transporters, which lead to the expulsion of cellular drug contents. Thymoquinone (TQ) is a bioactive molecule with anticancer as well as anti-inflammatory activities via the downregulation of several chemokines and cytokines. Nevertheless, the pharmacological importance and therapeutic feasibility of thymoquinone are underutilized due to intrinsic pharmacokinetics, including short half-life, inadequate biological stability, poor aqueous solubility, and low bioavailability. Owing to these pharmacokinetic limitations of TQ, nanoformulations have gained remarkable attention in recent years. Therefore, this compilation intends to critically analyze recent advancements in rheumatoid arthritis and cancer delivery of TQ. This literature search revealed that nanocarriers exhibit potential results in achieving targetability, maximizing drug internalization, as well as enhancing the anti-inflammatory and anticancer efficacy of TQ. Additionally, TQ-NPs (thymoquinone nanoparticles) as a therapeutic payload modulated autophagy as well as enhanced the potential of other drugs when given in combination. Moreover, nanoformulations improved pharmacokinetics, drug deposition, using EPR (enhanced permeability and retention) and receptor-mediated delivery, and enhanced anti-inflammatory and anticancer properties. TQ’s potential to reduce metal toxicity, its clinical trials and patents have also been discussed.

2010 ◽  
Vol 10 ◽  
pp. 2248-2253 ◽  
Author(s):  
Xiao Hua Pan ◽  
Jianxin Zhang ◽  
Xiaowei Yu ◽  
Ling Qin ◽  
Ligeng Kang ◽  
...  

Due to the complex etiology of rheumatoid arthritis (RA), it is difficult to be completely cured at the current stage although many approaches have been applied in clinics, especially the wide application of nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). New drug discovery and development via the recently discovered cholinergic anti-inflammatory and antinociceptive pathways should be promising. Based on the above, the nicotinic acetylcholine receptor agonists maintain the potential for the treatment of RA. Therefore, new therapeutic approaches may rise from these two newly discovered pathways. More preclinical experiments and clinical trials are required to confirm our viewpoint.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 862.2-863
Author(s):  
M. K. Chung ◽  
J. S. Park ◽  
H. S. Lim ◽  
C. H. Lee ◽  
J. Lee

Background:Rheumatoid arthritis (RA) predominantly affects women and has a significant impact on childbearing. Several population-based studies identifying incidence, prevalence, and medication use of RA have been reported, yet epidemiological studies focusing on women with RA in childbearing years are missing.Objectives:We aimed to identify the incidence, prevalence and medication use of RA among Korean women in childbearing years.Methods:From National Health Insurance Service (NHIS) data (2009-2016), containing inpatient and outpatient claim information for approximately 97% of the Korean population, we identified 9,217,139 women aged between 20-44 years. Incidence and prevalence of RA in the specific sociodemographic group of women in childbearing age were analyzed, and the prevalence of medication prescription were compared between women with RA and controls without rheumatic diseases such as RA, systemic lupus erythematosus, and ankylosing spondylitis. Individuals with RA were defined by the presence of International Classification of Disease, 10th revision code, M05. The medication use was defined as receiving > 90days prescriptions of NSAIDs, corticosteroids (CSs), and conventional synthetic (cs) disease modifying antirheumatic drugs (DMARDs) or > 1day prescription of biologic (b) DMARDs.Results:Total 24,590 women with RA were identified. The average incidence of RA during 2011-2016 among women in childbearing years was 24.1/100,000 person-years (PYs) (95% CI 20.91-27.31) with a yearly increase from 20.99/100,000 PYs in 2011 to 28.38/100,000 PYs in 2016. The average prevalence of RA during 2009-2016 among women in childbearing years was 105.2/100,000 PYs (95% CI 99.0-111.5) with a minimum of 95.7/100,000 PYs in 2009 and a maximum of 110.5/100,000 PYs in 2016. There were increasing trends in both incidence and prevalence of RA according to age among women in childbearing years peaking in the age group of 40-44 years. The prescriptions of NSAIDs, CSs, csDMARDs and bDMARDs were more frequent in women with RA than controls (NSAIDs; 94.21% vs 21.79%, CSs; 83.65% vs 4.28%, csDMARDs; 91.23% vs 0.41%, bDMARDs; 0.11% vs 0%, p<0.001).Conclusion:The incidence and prevalence of RA are high among Korean women in childbearing years, and medication use was significantly more frequent in this specific population than controls. High disease burden is imposed upon women in childbearing years.References:[1] Won S, Cho SK, Kim D, Han M, Lee J, Jang EJ, Sung YK, Bae SC: Update on the prevalence and incidence of rheumatoid arthritis in Korea and an analysis of medical care and drug utilization. Rheumatol Int 2018, 38(4):649-656.[2] Smeele HTW, Dolhain R: Current perspectives on fertility, pregnancy and childbirth in patients with Rheumatoid Arthritis. Seminars in arthritis and rheumatism 2019, 49(3s):S32-s35.Table 1.Medication use among women with RA and controls in childbearing age between 20-44 years during 2009-2016Control(n=155,486)RA(n=23,756)n(%)n(%)PNSAIDs33,887(21.79)22,380(94.21)<.0001Steroids6,653(4.28)19,871(83.65)<.0001csDMARDs634(0.41)21,673(91.23)<.0001bDMARDs0(0.00)27(0.11)<.0001RA, rheumatoid arthritis; NSAID, non-steroidal anti-inflammatory drug; cs, conventional synthetic; b, biologic; DMARDs, disease modifying antirheumatic drugsDisclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1147.1-1147
Author(s):  
A. Haddouche ◽  
K. Ait Bellabas ◽  
W. F. Hamrani ◽  
S. Sahraoui ◽  
R. Fatma ◽  
...  

Background:The management of rheumatoid arthritis refractory to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) is currently well codified and includes different types of biologics and even targeted sDMARDs. A rotation of biologic therapies is recommended in order to better control the disease.Methods:We report the case of a 20-year-old patient followed in our hospital for the management of a deforming and erosive seropositive rheumatoid arthritis (FR +, ACPA +) with a juvenile onset at the age of 8 years. The diagnosis of an immunopositive polyarticular form of JIA was retained in 2010 (9 years old); the patient was treated with methotrexate (MTX) at a dose of 10 mg per week and methylprednisolone at doses varying between 4 and 10 mg per day. Following the failure of MTX, etanercept was introduced for 6 months without success, followed by tocilizumab in 2012 at a dose of 8mg/kg/month for a year, without good response. In 2014, a course of rituximab (RTX) at a dose of 2 shots of 500mg, 2 weeks apart was prescribed followed 9 months later by etanercept at a dose of 50 mg a week for 3 years then by adalimumab (40mg/ week) because of the multiple treatment failures.In 2018, the repetition of RTX at a dose of 1g, renewed 15 days later, improved the patient for only 3 months. Then, a combination of two biologics, namely RTX (2 x 1g, 15 days apart) and adalimumab 1 month later (40mg / week) was received by the patient with a good response at 3 months. The latter was maintained for 7 months even after stopping the adalimumab following confinement for COVID-19. In September 2020, flares occurred and the adalimumab (ADA) has been delivered but without success during 3 months, stopped later for a benign form of COVID-19 (15 months after RTX). In January 2021, the association RTX + ADA was given again and we hope that it will be as effective as the first prescription.Results:The clinical and biological severity of our patient’s rheumatoid arthritis led us to give a combination of two biological treatments. Indeed, we do not have other therapeutic classes to deliver to her, that encouraged us to rotate between all the available biological therapies in our country. The combination of a CD20 inhibitor (RTX) with a TNF blocker (ADA) was safe and made possible, for the first time, the achievement of clinical and biological remission during 7 months, even after stopping the TNF blocker. Greenwald et al. reported the safety of the combination of RTX + TNF inhibitors in a randomized clinical trial in 51 patients. Its efficacy, a secondary goal of the study, was suggested at 24 weeks by the percentage of ACR 20 and ACR 50 responses that was greater than in the RTX placebo group.Conclusion:The combination of RTX with a TNF blocker can be a real alternative therapy in rheumatoid arthritis with failure to a biological monotherapy.Disclosure of Interests:None declared


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