scholarly journals Hyaluronic Acid Coated Acid-Sensitive Nanoparticles for Targeted Therapy of Adjuvant-Induced Arthritis in Rats

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 146 ◽  
Author(s):  
Changhui Yu ◽  
Xiangyu Li ◽  
Yufei Hou ◽  
Xiangxue Meng ◽  
Deli Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Therapy ◽  
Zeta Potential ◽  
Polymeric Nanoparticles ◽  
Vital Role ◽  
Activated Macrophages ◽  
Acid Sensitivity ◽  
Adjuvant Induced Arthritis

Activated macrophages play a vital role in rheumatoid arthritis (RA) pathophysiology. CD44 is an overexpressed receptor on activated macrophages that is a potential target site for RA treatment. In this study, we prepared hyaluronic acid (HA) coated acid-sensitive polymeric nanoparticles (HAPNPs) composed of egg phosphatidylcholine, polyethylenimine, and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) loaded with dexamethasone (Dex) for the treatment of RA. PCADK was used to form polymeric cores because of its acid-sensitivity. The HAPNPs were about 150 nm in size and had a zeta potential of −2.84 mV. The release rate of Dex from HAPNPs/Dex in vitro increased markedly when the pH decreased from 7.4 to 4.5, indicating that the HAPNPs were pH-sensitive. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages treated with HAPNPs, suggesting that HAPNPs could be effective nanodevices target to activated macrophages. In rats with adjuvant-induced arthritis, HAPNPs could inhibited the progression of RA. Taken together, these results suggest that the HAPNPs could be useful in RA therapy.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals Antioxidant-Loaded Mucoadhesive Nanoparticles for Eye Drug Delivery: A New Strategy to Reduce Oxidative Stress

Processes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 379
Author(s):  
Sandra Cordeiro ◽  
Beatriz Silva ◽  
Ana Margarida Martins ◽  
Helena Margarida Ribeiro ◽  
Lídia Gonçalves ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hyaluronic Acid ◽  
Zeta Potential ◽  
Retinal Pigment ◽  
Release Kinetic ◽  
Efficient Treatment ◽  
Non Invasive ◽  
Diffusion Cells ◽  
Franz Diffusion Cells

There are several approaches to treat ocular diseases, which can be invasive or non-invasive. Within the non-invasive, new pharmaceutical strategies based on nanotechnology and mucoadhesive polymers are emerging methodologies, which aim to reach an efficient treatment of eye diseases. The aim of this work was the development of novel chitosan/hyaluronic acid nanoparticle systems with mucoadhesive properties, intended to encapsulate antioxidant molecules (e.g., crocin) aiming to reduce eye oxidative stress and, consequently, ocular disease. An ultraviolet (UV) absorber molecule, actinoquinol, was also added to the nanoparticles, to further decrease oxidative stress. The developed nanoparticles were characterized and the results showed a mean particle size lower than 400 nm, polydispersity index of 0.220 ± 0.034, positive zeta potential, and high yield. The nanoparticles were also characterized in terms of pH, osmolality, and viscosity. Mucoadhesion studies involving the determination of zeta potential, viscosity, and tackiness, showed a strong interaction between the nanoparticles and mucin. In vitro release studies using synthetic membranes in Franz diffusion cells were conducted to unravel the drug release kinetic profile. Ex vitro studies using pig eye scleras in Franz diffusion cells were performed to evaluate the permeation of the nanoparticles. Furthermore, in vitro assays using the ARPE-19 (adult retinal pigment epithelium) cell line showed that the nanoparticles can efficiently decrease oxidative stress and showed low cytotoxicity. Thus, the developed chitosan/hyaluronic acid nanoparticles are a promising system for the delivery of antioxidants to the eye, by increasing their residence time and controlling their delivery.

A hyaluronic acid–methotrexate conjugate for targeted therapy of rheumatoid arthritis

2014 ◽  
Vol 50 (57) ◽  
pp. 7632 ◽  
Author(s):  
Jung Min Shin ◽  
Seol-Hee Kim ◽  
Thavasyappan Thambi ◽  
Dong Gil You ◽  
Jueun Jeon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Therapy

scholarly journals Folate Receptor-Targeting and Reactive Oxygen Species-Responsive Liposomal Formulation of Methotrexate for Treatment of Rheumatoid Arthritis

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 582 ◽  
Author(s):  
Chen ◽  
Amerigos J.C. ◽  
Su ◽  
Guissi ◽  
Xiao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Drug Release ◽  
Cellular Uptake ◽  
Folate Receptor ◽  
Oxygen Species ◽  
Activated Macrophages

Multifunctional nanomedicines with active targeting and stimuli-responsive drug release function utilizing pathophysiological features of the disease are regarded as an effective strategy for treatment of rheumatoid arthritis (RA). Under the inflammatory environment of RA, activated macrophages revealed increased expression of folate receptor and elevated intracellular reactive oxygen species (ROS) level. In this study, we successfully conjugated folate to polyethylene glycol 100 monostearate as film-forming material and further prepared methotrexate (MTX) and catalase (CAT) co-encapsulated liposomes, herein, shortened to FOL-MTX&CAT-L, that could actively target to activated macrophages. Thereafter, elevated intracellular hydrogen peroxide, the main source of ROS, diffused into liposomes and encapsulated CAT catalyzed the decomposition of hydrogen peroxide into oxygen and water. Continuous oxygen-generation inside liposomes would eventually disorganize its structure and release the encapsulated MTX. We characterized the in vitro drug release, cellular uptake and cytotoxicity studies as well as in vivo pharmacokinetics, biodistribution, therapeutic efficacy and safety studies of FOL-MTX&CAT-L. In vitro results revealed that FOL-MTX&CAT-L possessed sufficient ROS-sensitive drug release, displayed an improved cellular uptake through folate-mediated endocytosis and exhibited a higher cytotoxic effect on activated RAW264.7 cells. Moreover, in vivo results showed prolonged blood circulation time of PEGylated liposomes, enhanced accumulation of MTX in inflamed joints of collagen-induced arthritis (CIA) mice, reinforced therapeutic efficacy and minimal toxicity toward major organs. These results imply that FOL-MTX&CAT-L may be used as an effective nanomedicine system for RA treatment.

scholarly journals Andrographolide Ameliorates Rheumatoid Arthritis by Regulating the Apoptosis–NETosis Balance of Neutrophils

2019 ◽  
Vol 20 (20) ◽  
pp. 5035 ◽  
Author(s):  
Xiaohong Li ◽  
Kai Yuan ◽  
Qingqing Zhu ◽  
Qingyi Lu ◽  
Haixu Jiang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Neutrophil Infiltration ◽  
Chronic Inflammatory Disease ◽  
Adjuvant Induced Arthritis ◽  
Extracellular Traps ◽  
Ankle Joints ◽  
Activated Neutrophils ◽  
Labdane Diterpenoid ◽  
Anti Inflammation

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis with swelling and pain at synovial joints. In RA patients, delayed neutrophil apoptosis amplifies the inflammatory response and massively released neutrophil extracellular traps (NETs) induce tissue damage and provide self-antigens. Andrographolide (AD) is the major active labdane diterpenoid derived from Andrographis paniculata, which has multiple pharmacological effects, including hepatoprotection, anti-angiogenesis, anti-thrombosis, and anti-inflammation. In the present study, we investigated the effect of AD on an adjuvant-induced arthritis (AA) murine model of RA and found that AD alleviated murine arthritis by reducing neutrophil infiltration and NETosis in the ankle joints and relieved the systematic inflammation. In vitro experiments showed that AD accelerated the apoptosis of lipopolysaccharide-activated neutrophils and inhibited autophagy-dependent extracellular traps formation of neutrophils. These findings suggest that AD has considerable potential for RA therapy.

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.

MiR-1246 Involves in the Proliferation, Apoptosis and Inflammation of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Targeting Axis Inhibition Protein 2 and Glycogen Synthetase Kinase-3β via Wnt/β-Catenin Pathway in Rheumatoid Arthritis

2021 ◽  
Vol 11 (11) ◽  
pp. 2246-2253
Author(s):  
Siyin Guo ◽  
Shichang Hu ◽  
Guoyuan Zhao ◽  
Weijian Hu ◽  
Yiling Liao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Bioinformatic Analysis ◽  
Vital Role ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Regulatory Effects ◽  
Apoptosis And Inflammation

Background and Objective: Accumulating evidence supports that fibroblast-like synovial cells (FLS) plays a vital role in the pathogenesis of rheumatoid arthritis (RA). miR-1246 has been reported to be up-regulated in the sera of RA patients. The purpose of the present research was to determine the potential role of miR-1246 in RA and the underlying mechanisms. Methods: miR-1246, GSK3β and AXIN2 levels were determined by RT-qPCR. By exploiting miR-1246 inhibitor, shRNA-GSK3β and shRNA-AXIN2, we detected the effects of miR-1246, GSK3β and AXIN2 on cell proliferation, apoptosis and inflammation in RA-FLSs. Bioinformatics analysis predicted the binding sites of miR-1246 to AXIN2, miR-1246 to GSK3β. Moreover, luciferase reporter assay verified the binding relationship. Results: In comparison with normal human FLSs, higher levels of miR-1246 existed in RA-FLSs. Downregulation of miR-1246 inhibited cell proliferation, inflammation and β-catenin expression, and promoted cell apoptosis. Furthermore, bioinformatic analysis and dual-luciferase reporter assay identified AXIN2 or GSK3β as a target gene of miR-1246. Downregulation of miR-1246 enhanced AXIN2 and GSK3β expression in RA-FLSs. Besides, co-transfection with shRNA-GSK3β or shRNA-AXIN2 partly reversed the regulatory effects of miR-1246 inhibitor in RA-FLSs. Conclusions: Collectively, our in vitro experiments proved that downregulation of miR-1246 might alleviate RA pathogenesis by targeting AXIN2 and GSK3β via Wnt/β-Catenin axis.

scholarly journals PREPARATION AND EVALUATION OF SULFASALAZINE LOADED SODIUM ALGINATE MICROBEADS FOR SUSTAINED DELIVERY

2016 ◽  
pp. 72
Author(s):  
Krishna Sailaja A ◽  
Jyothika Mattam
Keyword(s):  
Rheumatoid Arthritis ◽  
Side Effects ◽  
Drug Release ◽  
Zeta Potential ◽  
Sodium Alginate ◽  
Process Parameters ◽  
Megaloblastic Anemia ◽  
Entrapment Efficiency ◽  
Sustained Delivery

<p>ABSTRACT<br />Objective: The main objective of the work was to prepare and evaluate sulfasalazine loaded sodium alginate microbeads for sustained delivery for<br />the treatment of inflammatory bowel disease and rheumatoid arthritis. Sulfasalazine has crystalluria, thrombocytopenia, and megaloblastic anemia<br />as side effects, so to reduce side effect microbeads were prepared.<br />Methods: The sulfasalazine microbeads were prepared by inotropic gelation method by optimizing process parameters such as concentration of<br />calcium chloride, agitation speed, and time of agitation. The concentration of polymer sodium alginate was varied.<br />Result: Among the five formulations, the best formulation was considered by comparing process parameters such as the entrapment efficiency, drug<br />content, in vitro drug release studies, scanning electron microscope analysis, and zeta potential.<br />Conclusion: On comparison, B3 formulation was considered as best formulation with a mean particle size ranging from 40.9 to 244 µm, drug content<br />of 94.7%, entrapment efficiency of 87.7%, and the drug release was found to be 97.1% for 12 hrs and followed zero order kinetics and non-Fickian<br />diffusional pathway, with a zeta potential value of −56.8 mV indicating higher stability.<br />Keywords: Inotropic gelation method, Sodium alginate, Microbeads, Rheumatoid arthritis, Side effects.</p>

Hyaluronic acid-modified betamethasone encapsulated polymeric nanoparticles: fabrication, characterisation, in vitro release kinetics, and dermal targeting

2018 ◽  
Vol 9 (2) ◽  
pp. 520-533 ◽  
Author(s):  
Manisha Pandey ◽  
Hira Choudhury ◽  
Tarakini A. P. Gunasegaran ◽  
Saranyah Shanmugah Nathan ◽  
Shadab Md ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Polymeric Nanoparticles ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Vitro Release

scholarly journals Hyaluronic acid Hydrogels Hybridized with Au-Triptolide Nanoparticle for Intra-articular targeted multi-therapy of Rheumatoid Arthritis

2022 ◽  
Author(s):  
Chenxi Li ◽  
Rui Liu ◽  
Yurong Song ◽  
Dongjie Zhu ◽  
Liuchunyang Yu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gold Nanoparticles ◽  
Hyaluronic Acid ◽  
Near Infrared ◽  
Mtor Pathway ◽  
Collagen Induced Arthritis ◽  
Hybrid Hydrogels ◽  
Low Dosage

Abstract Triptolide (TP) is a DMARD highly effective in patients with RA. Hyaluronic acid (HA) hydrogels loaded RGD-attached gold nanoparticles containing TP were synthesized to alleviate the toxicity and increase therapeutic specificity. The hydrogels can be applied for targeted photothermal-chemo therapy, and in vivo imaging of RA. Heat was locally generated at the inflammation site after degradation of HA chains due to near-infrared resonance (NIR) irradiation of gold nanoparticles (AuNPs), and TP was released. Administration of the hybrid hydrogels containing low dosage of TP combined with NIR irradiation alleviated arthritic conditions and improved the inflamed joint in collagen-induced arthritis (CIA) mice. In vitro effect of the hydrogel was mediated through decrease of phosphorylation of mTOR and its substrate, p70S6K1, thus inhibiting mTOR pathway.

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