Topical delivery of curcumin-loaded transfersomes gel ameliorated rheumatoid arthritis by inhibiting NF-κβ pathway

Nanomedicine ◽  
2021 ◽  
Author(s):  
Eleesha Sana ◽  
Mahira Zeeshan ◽  
Qurat Ul Ain ◽  
Ashraf Ullah Khan ◽  
Irshad Hussain ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Delivery ◽  
Therapeutic Efficacy ◽  
Skin Penetration ◽  
Sustained Drug Release ◽  
In Vitro Techniques ◽  
Dermal Tissue ◽  
Pro Inflammatory Cytokines

Aim: To fabricate and evaluate curcumin-loaded transfersomes (Cur-TF) for the targeted delivery and enhanced therapeutic efficacy of curcumin for the treatment of rheumatoid arthritis (RA). Methods: Modified thin-film hydration method was used to prepare Cur-TF which were then embedded into carbopol-934 gel. They were further evaluated through in vitro techniques and in an in vivo arthritis model. Results: Cur-TF had optimal particle size, spherical morphology, high encapsulation efficiency and sustained drug release profiles. The Cur-TF gel had better in vitro skin penetration than plain curcumin. In vivo findings demonstrated improved clinical, histological and x-ray scores and reduced pro-inflammatory cytokines through NF-κβ inhibition. Conclusion: Cur-TF gel delivered curcumin to the arthritic dermal tissue through a topical route and demonstrated promising therapeutic efficacy by significantly alleviating complete Freud's adjuvant (CFA)-induced arthritis.

Intra-articular Administrated Hydrogels of Hyaluronic Acid Hybridized with Triptolide/Gold Nanoparticles for Targeted Delivery to Rheumatoid Arthritis Combined with Photothermal-chemo Therapy

2021 ◽  
Author(s):  
Chenxi Li ◽  
Rui Liu ◽  
Yurong Song ◽  
Dongjie Zhu ◽  
Liuchunyang Yu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
Near Infrared ◽  
Invasion And Migration ◽  
Nir Light ◽  
Hybrid Hydrogels ◽  
And Migration

Abstract Triptolide (TP) as a disease-modifying anti-rheumatic drug (DMARD) is effective on the treatment of rheumatoid arthritis (RA). To alleviate the toxicity and elevate therapeutic specificity, hyaluronic acid (HA) hydrogels load RGD-attached gold nanoshell containing TP are synthesized, which can be used for targeted photothermal-chemo therapy, and imaging of RA in vivo. The hydrogels system composed of thiol and tyramine modified HA conjugates has been applied artificial tissue models of cartilage for studying drug delivery and release properties. After the degradation of HA chains, heat together with drugs can be delivered to the inflammatory joints simultaneously due to the near-infrared resonance (NIR) irradiation of Au nanoshell. RA is a chronic inflamed disease, which is characterized by synovial inflammation of multiple joints, and can be penetrated with NIR light. These intra-articular administrated hybrid hydrogels combined with NIR irradiation can improve clinical arthritic conditions and inflamed joints in collagen-induced arthritis (CIA) mice, which just need a smaller dosage of TP with non-toxicity. Additionally, the TP-Au/HA hybrid hydrogels treatment reduced the invasion and migration of RA fibroblast-like synoviocytes (RA-FLSs) in vitro significantly, through reducing the phosphorylation of mTOR and p70S6K, its substrates, and confirmed that the mTOR pathway was inhibited.

scholarly journals Breast Cancer and Microcalcifications: An Osteoimmunological Disorder?

2020 ◽  
Vol 21 (22) ◽  
pp. 8613
Author(s):  
Alisson Clemenceau ◽  
Laetitia Michou ◽  
Caroline Diorio ◽  
Francine Durocher
Keyword(s):  
Breast Cancer ◽  
Rheumatoid Arthritis ◽  
Inflammatory Cytokines ◽  
Breast Cancer Incidence ◽  
Biological Agents ◽  
Breast Cancer Cell Lines ◽  
Molecular Characteristics ◽  
Pro Inflammatory Cytokines

The presence of microcalcifications in the breast microenvironment, combined with the growing evidences of the possible presence of osteoblast-like or osteoclast-like cells in the breast, suggest the existence of active processes of calcification in the breast tissue during a woman’s life. Furthermore, much evidence that osteoimmunological disorders, such as osteoarthritis, rheumatoid arthritis, or periodontitis influence the risk of developing breast cancer in women exists and vice versa. Antiresorptive drugs benefits on breast cancer incidence and progression have been reported in the past decades. More recently, biological agents targeting pro-inflammatory cytokines used against rheumatoid arthritis also demonstrated benefits against breast cancer cell lines proliferation, viability, and migratory abilities, both in vitro and in vivo in xenografted mice. Hence, it is tempting to hypothesize that breast carcinogenesis should be considered as a potential osteoimmunological disorder. In this review, we compare microenvironments and molecular characteristics in the most frequent osteoimmunological disorders with major events occurring in a woman’s breast during her lifetime. We also highlight what the use of bone anabolic drugs, antiresorptive, and biological agents targeting pro-inflammatory cytokines against breast cancer can teach us.

scholarly journals Folate-conjugated hydrophobicity modified glycol chitosan nanoparticles for targeted delivery of methotrexate in rheumatoid arthritis

2020 ◽  
Vol 18 ◽  
pp. 228080002096262 ◽  
Author(s):  
Zhongqing Wu ◽  
Kanna Xu ◽  
Jikang Min ◽  
Minchang Chen ◽  
Liping Shen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Delivery ◽  
Chitosan Nanoparticles ◽  
Autoimmune Disorder ◽  
Glycol Chitosan ◽  
Hydrophobically Modified ◽  
Superior Efficacy ◽  
Transmission Electron

Background: Targeted delivery to the Rheumatoid arthritis (RA) which is characterized by destruction and degeneration of bones due to chronic inflammation is of great need. RA being a chronic autoimmune disorder might result in severe disability and morbidity. A targeted delivery system is designed to deliver methotrexate (MTX) for RA. Methods: Here, we synthesized folic acid (FA) conjugated hydrophobically modified glycol chitosan (GC) self-assembled nanoparticles (FA-GC-SA) for the targeted delivery of MTX to RA. The FA conjugation and hydrophobic modification of GC by stearic acid (SA) was confirmed by Fourier-transform infrared spectroscopy (FTIR). The FA-GC-SA was exploited for developing targeted nanoparticles encapsulating MTX by the ionic gelation method. The particles were characterized and evaluated for their targeting potential in in vitro cell culture studies. Further their in vivo efficacy in arthritis induced rats using collagen was also evaluated. Results: FTIR confirms the successful modification of GC-SA and FA-GC-SA. The FA-GC-SA-MTX of size 153 ± 9 nm were prepared with high encapsulation efficiency of MTX. The FA-GC-SA-MTX size was further confirmed by transmission electron microscopy (TEM). In vitro cell studies revealed the superior efficacy of FA-GC-SA-MTX in cell cytotoxicity. Also, significantly higher cellular uptake of FA functionalized FA-GC-SA-MTX was observed in comparison to non-functionalized GC-SA-MTX attributed to folate receptors (FRs) mediated endocytosis. In vivo results confirms the potential of FA-GC-SA-MTX which reduces reduces the pro-inflammatory cytokines, paw thickness, and arthritis score in collagen induced rats. Conclusion: The results shows that FRs targeted FA-GC-SA-MTX has superior efficacy in the treatment of RA.

scholarly journals New horizons of methotrexate application

2020 ◽  
Vol 17 (1) ◽  
pp. 20-26
Author(s):  
Vladimir Maksimović ◽  
Svetlana Goločorbin-Kon ◽  
Momir Mikov ◽  
Jelena Cvejić ◽  
Zora Pavlović-Popović ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Bowel Disease ◽  
Anticancer Drug ◽  
Bowel Disease ◽  
Targeted Delivery ◽  
Inflammatory Diseases ◽  
New Horizons ◽  
Inflammatory Bowel

Methotrexate is an anti-inflammatory and anticancer drug that has been used in the treatment of various oncological and inflammatory diseases (such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, sarcoidosis, etc.). Scientists are working on finding optimal formulation that will maintain its efficacy and improve safety and nanoparticles have shown to be carriers with great potential as they protect the drug from degradation while at the same time they increase absorption. In vivo and in vitro studies of numerous nanoparticle preparations have showed that they generally have appropriate characteristics and can be carriers for targeted delivery of methotrexate to the tissues affected by disease. Topical preparations of methotrexate, mainly for the treatment of psoriasis, have also been assessed in various research and have showed promising results. Further research is warranted by the obtained results and will hopefully lead to new methotrexate formulations that will be approved by regulatory authorities and used instead of existing ones to improve efficacy of the drug and patients' safety.

Morphometrical estimation of fetal heart growth at different gestational ages by In vivo and In vitro techniques

2011 ◽  
Vol 3 (5) ◽  
pp. 491-494
Author(s):  
Dr. Haritha Kumari Nimmagadda ◽  
◽  
Pooja Pant Pooja Pant ◽  
Rajeev Mukhia ◽  
Dr. Aruna Mukherjee
Keyword(s):  
Fetal Heart ◽  
In Vitro Techniques

Internal and External Triggering Mechanism of “Smart” Nanoparticle-Based DDSs in Targeted Tumor Therapy

2018 ◽  
Vol 24 (15) ◽  
pp. 1639-1651 ◽  
Author(s):  
Xian-ling Qian ◽  
Jun Li ◽  
Ran Wei ◽  
Hui Lin ◽  
Li-xia Xiong
Keyword(s):  
Targeted Delivery ◽  
Tumor Therapy ◽  
Burst Release ◽  
Tumor Site ◽  
Chemotherapeutic Drugs ◽  
Triggering Mechanism ◽  
Triggering Factors ◽  
Or Genes

Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: “passive”, “active”, and “smart” targeting. Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis of findings from in vivo and in vitro studies. Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of “smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

Comparison of In Vitro and In Vivo Effects of Infliximab on Cytokine Production in Proliferating CD4+ T Cells in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 1 (2) ◽  
pp. 122-128
Author(s):  
Syuichi Koarada ◽  
Yuri Sadanaga ◽  
Natsumi Nagao ◽  
Satoko Tashiro ◽  
Rie Suematsu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production

scholarly journals Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1456
Author(s):  
Isabel Matos Oliveira ◽  
Cristiana Gonçalves ◽  
Myeong Eun Shin ◽  
Sumi Lee ◽  
Rui Luis Reis ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mechanical Properties ◽  
Silk Fibroin ◽  
Therapeutic Efficacy ◽  
Composite Structures ◽  
Gelation Time ◽  
Polymeric Materials ◽  
Gellan Gum ◽  
Traditional Use

Rheumatoid arthritis is a rheumatic disease for which a healing treatment does not presently exist. Silk fibroin has been extensively studied for use in drug delivery systems due to its uniqueness, versatility and strong clinical track record in medicine. However, in general, natural polymeric materials are not mechanically stable enough, and have high rates of biodegradation. Thus, synthetic materials such as gellan gum can be used to produce composite structures with biological signals to promote tissue-specific interactions while providing the desired mechanical properties. In this work, we aimed to produce hydrogels of tyramine-modified gellan gum with silk fibroin (Ty–GG/SF) via horseradish peroxidase (HRP), with encapsulated betamethasone, to improve the biocompatibility and mechanical properties, and further increase therapeutic efficacy to treat rheumatoid arthritis (RA). The Ty–GG/SF hydrogels presented a β-sheet secondary structure, with gelation time around 2–5 min, good resistance to enzymatic degradation, a suitable injectability profile, viscoelastic capacity with a significant solid component and a betamethasone-controlled release profile over time. In vitro studies showed that Ty–GG/SF hydrogels did not produce a deleterious effect on cellular metabolic activity, morphology or proliferation. Furthermore, Ty–GG/SF hydrogels with encapsulated betamethasone revealed greater therapeutic efficacy than the drug applied alone. Therefore, this strategy can provide an improvement in therapeutic efficacy when compared to the traditional use of drugs for the treatment of rheumatoid arthritis.

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