Downregulation of pro-inflammatory markers IL-6 and TNF-α in rheumatoid arthritis using nano-lipidic carriers of a quinone-based phenolic: an in vitro and in vivo study.

Rheumatoid arthritis (RA) is a joint ailment with multi-factorial immune-mediated degenerative pathogenesis, including genetic and environmental defects. Resistance to disease-modifying anti-rheumatic drugs (DMARDs) happens due to excessive drug efflux over time, rendering the concentration insufficient to elicit a response. Thymoquinone (TQ) is a quinone-based phenolic compound with antioxidant and anti-inflammatory activities that downregulate numerous pro-inflammatory cytokines. However, its pharmaceutical importance and therapeutic utility are underexplored due to intrinsic physicochemical characteristics such as inadequate biological stability, short half-life, low hydrophilicity, and less systemic availability. Tamanu oil-stabilised nanostructured lipid carriers (TQ-NLCs) were prepared and optimised using Box-Behnken design (BBD) with the size of 153.9 ± 0.52 nm and surface charge of -30.71 mV. The % entrapment efficiency and drug content were found to be 84.6 ± 0.50% and 14.75 ± 0.52%, respectively. Furthermore, the TQ-loaded NLCs (TQ-NLCs) assayed for skin permeation for transdermal delivery which significantly (p < 0.05) increased skin enhancement ratio 14.6 times compared to the aqueous solution of TQ. Tamanu oil displayed the synergistic anti-inflammatory potential with TQ in comparison to pure TQ, as evidenced against carrageenan (CRG)-induced paw oedema model and Freund's adjuvant-induced arthritic model. The arthritic and X-ray scores significantly (p < 0.05) reduced in TQ-NLCs and standard formulation-treated groups. Moreover, serum pro-inflammatory marker TNF-α and IL-6 levels were also significantly (p < 0.05) reduced in TQ-NLCs gel-treated group compared to the arthritic control group.

Recent Findings on Thymoquinone and Its Applications as a Nanocarrier for the Treatment of Cancer and Rheumatoid Arthritis.

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.

Synthesis of pH-sensitive crosslinked guar gum-g-poly(acrylic acid-co-acrylonitrile) for the delivery of thymoquinone against inflammation.

The present work aims to synthesize the pH-sensitive crosslinked guar gum-g-poly(acrylic acid-co-acrylonitrile) [guar-g-(AA-co-ACN)] via microwave-assisted technique for the sustained release of thymoquinone. The synthesized material [guar-g-(AA-co-ACN)] was optimized by varying synthetic parameters viz. monomer concentration, reaction time, and microwave power to obtain the maximum yield of the crosslinked guar gum grafted product as well as maximum encapsulation of thymoquinone. The synthesized material [guar-g-poly(AA-co-ACN)] was characterized by FT-IR, SEM, XRD, NMR, zeta potential, and thermal techniques. This synthesized material was used to encapsulate thymoquinone (TQ) for effective nanotherapeutic delivery. In-vitro thymoquinone release behavior of guar-g-poly(AA-co-ACN) based nanoparticles (NpTGG) was investigated. The maximum thymoquinone release (78%) was achieved at pH 7.4 and time (6 h). The NpTGG also exhibited better antioxidant activity and hemocompatibility as compared to thymoquinone. Cytotoxicity of uar-g-(AA-co-ACN) and NpTGG was also evaluated against the human kidney VERO cell line and found to be nontoxic. Current research provides a cost-effective and green approach for the synthesis of guar-g-(AA-co-ACN) and NpTGG for sustained release of thymoquinone.