Synergistic metabolic modulation of fibroblast-like synoviocytes via targeted dual prodrug nanoparticles to mitigate rheumatoid arthritis DOI Creative Commons
Shaobing Li, Jun‐Tao Lin, Chengxinqiao Wang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 15(1), P. 542 - 556

Published: Nov. 18, 2024

Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy inhibiting single target FLS using small molecular inhibitors limited for RA treatment. Herein, synergistic inhibition FLS' survival, proliferation, and activation by combining two inhibitors, diclofenac (DC) lonidamine (LND) was first verified. Subsequently, DC LND were individually conjugated to cystamine-modified hyaluronic acid (HA) prepare polymer-prodrug conjugates. A HAP-1 peptide-modified dual conjugates-assembled nanoparticles system (HAP-1NPDC+LND) further tailored optimal ratio targeted metabolic modulation alleviate symptoms. Upon uptake inflamed joints, HAP-1NPDC+LND released within intracellular reductive microenvironment, where hinders suppresses glycolytic enzymes eliminate synergistically. Additionally, secretion lactic pro-inflammatory factors from reduced, thereby disrupting crosstalk between macrophages. Finally, demonstrated promising mouse model collagen-induced (CIA). Overall, this research provides valuable insights into novel therapeutic strategies safe effective treatment through FLS.

Language: Английский

Polymeric nanoparticles-based targeted delivery of drugs and bioactive compounds for arthritis management DOI Creative Commons
Tanu Dixit, Anuradha Vaidya, Selvan Ravindran

et al.

Future Science OA, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 20, 2025

This review explores the potential of polymeric nanoparticles (PNPs) as targeted drug delivery systems for arthritic treatment, overcoming limitations present therapy. A thorough literature search was conducted on databases PubMed, Scopus, and Web Science to find published articles use in treatment arthritis. includes synthesis methods, mechanisms delivery, applications PNPs. Polymeric showed excellent promise management arthritis through enhanced stability drugs, controlled sustained release, reduced systemic side effects. Some highlighted biocompatible targeting capabilities natural synthetic polymers include chitosan, hyaluronic acid, PLGA. Bioactive compounds such curcumin resveratrol delivered by PNPs therapeutic efficacy preclinical models. Despite their promise, challenges rapid clearance manufacturing scalability remain critical barriers. offer a transformative approach enabling targeted, sustained, safe delivery. Translation into clinical would thus require developments nanoparticle design, personalized medicine, scalable production techniques.

Language: Английский

Citations

1
Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights DOI Creative Commons
Mislav Radić, Andrej Belančić, Hana Đogaš

et al.

Antibiotics, Journal Year: 2025, Volume and Issue: 14(1), P. 65 - 65

Published: Jan. 10, 2025

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) biologics, some patients remain refractory to conventional treatments. Tetracyclines, such as minocycline doxycycline, exhibit anti-inflammatory immunomodulatory properties, making them potential supplementary This narrative review explores their effectiveness, mechanisms of action, safety profiles, current challenges care. Tetracyclines have demonstrated significant effects, including the inhibition pro-inflammatory cytokines matrix metalloproteinases (MMPs), which are critical pathology. Clinical trials, double-blind, placebo-controlled studies, shown efficacy reducing symptoms, particularly early cases. However, use remains limited inconsistent evidence, small sample sizes, concerns about antimicrobial resistance. Current guidelines for do not explicitly recommend tetracyclines due these limitations, although off-label may be considered specific The tetracycline restricted drug interactions causing bacterial resistance alongside unpredictable patient responses, hence necessity prudence its prescription within clinical setting. To overcome development safer compounds, in-depth silico analyses, integration personalized medicine approaches needed. Overall, show promise adjunct therapies dual actions. highlights need further research address gaps modified reduced effects improved well optimize outcomes.

Language: Английский

Citations

0
Nanotechnology-Driven Drug Delivery in Rheumatoid Arthritis: Current Trends, Key Challenges, and Future Perspectives DOI Open Access
Minal Narkhede,

Shruti Nanaji Bhamare

Biosciences Biotechnology Research Asia, Journal Year: 2025, Volume and Issue: 22(1), P. 1 - 21

Published: March 25, 2025

ABSTRACT: Rheumatoid arthritis is a chronic autoimmune disorder that causes progressive joint damage and disability, significantly impacting patients' quality of life. In this Traditional treatment, including disease-modifying ant rheumatic drugs biologics often fall short in targeting the disease with precision, leading to side effects limited efficacy. We selected Nanotechnology which offers promising solution for improving drug delivery enhancing therapeutic outcomes RA management. This review explores current trends future prospects nanotechnology-based systems treatment. discuss various types nanocarriers, such as nanoparticles, liposomes, micelles, their ability enhance targeted biologic agents small molecules. Additionally, we examine potential "smart" nanomaterials respond disease-specific stimuli controlled release, thereby reducing systemic toxicity. The integration nanotechnology biologics, gene therapies, combination treatments highlighted strategy efficacy minimizing adverse effects. Finally, addresses ongoing challenges directions, need more extensive clinical trials ensure safety effectiveness these innovative therapies patients.

Language: Английский

Citations

0
Phytochemical, LC‐MS Studies, and Assessment of Antioxidant, Anti‐inflammatory, Hypoglycemic, Anti‐Rheumatoid‐arthritis Potential with Acmella paniculata: In‐Silico and In‐Vitro Appraisal DOI
Abu Md Ashif Ikbal, Avik Sarkar, Abhishek Saha

et al.

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(17)

Published: April 30, 2025

Abstract Acmella paniculata (AP), an ethnomedicinal plant, is valued for the management of pain, inflammation, arthritis, infection, diabetes and as tribal cuisine The study focused on validating AP against inflammatory rheumatoid arthritis (RA), hyperglycemia. Hydro‐ethanolic extract flower (HEFeAP) was prepared via maceration, followed by ultrasonication. Physicochemical characterization done using Thin Layer Chromatography (TLC), Liquid Chromatography‐Mass Spectrometry (LC‐MS), Ultra‐violet Spectroscopy (UV), Fourier Transform Infrared (FTIR). Major phytochemicals were assessed mediators molecular docking Molecular Dynamics (MD) simulations. antioxidant potential HEFeAP 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay (31.22 ± 0.53 µg mL −1 ) hydrogen peroxide (H₂O₂) scavenging (40.36 0.47 ). anti‐inflammatory activity, protective role RA, anti‐hyperglycaemic activities evaluated egg‐albumin denaturation, MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide) human‐fibroblast cells α‐amylase inhibition, showing IC 50 27.61, 65.75, 85.43 , respectively. Tumor Necrosis Factor‐alpha (TNF‐α), nitric‐oxide (NO) levels significantly downregulated in LPS‐stimulated PBMC‐derived macrophages (IC = 152 164.56 Phytochemical analysis revealed coumarins, flavonoids, polyphenols, steroids, local‐anaesthetic alkylamides. Active phytomolecules exhibited strong stable binding with biomarkers. These findings suggest can be used a candidate diabetes.

Language: Английский

Citations

0
Treatment of Rheumatoid Arthritis Based on the Inherent Bioactivity of Black Phosphorus Nanosheets DOI Creative Commons

Cheng Zhuang,

Ruiqi Sun,

Yuchen Zhang

et al.

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Rheumatoid arthritis (RA) is an autoimmune disease that affects the living quality of patients, especially elderly population. RA-related morbidity and mortality increase significantly with age, while current clinical drugs for RA are far from satisfactory may have serious side effects. Therefore, development new higher biosafety efficacy demanding. Black phosphorus nanosheets (BPNSs) been widely studied because their excellent biocompatibility. Here, we focus on inherent bioactivity BPNSs, report potential BPNSs as a therapeutic drug elucidate underlying mechanism. We find inhibit autophagy at early stage via AMPK-mTOR pathway, switch energy metabolic pathway to oxidative phosphorylation, intracellular ATP levels, suppress apoptosis, reduce inflammation stress, down-regulate senescence-associated secretory phenotype (SASP)-related genes in rheumatoid synovial fibroblasts (RA-SFs). Further, induce apoptosis macrophages promote transition M1 M2 by regulating related cytokines. Significantly, administration can alleviate key pathological features mice, revealing great potential. This study provides novel option treating RA, emerging promising candidate.

Language: Английский

Citations

1
Efficacy and safety of abatacept in preclinical rheumatoid arthritis: A systematic review and meta-analysis of randomized controlled trials DOI
Maheen Asif,

Aliza Asif,

Ummi Aiman Rahman

et al.

Seminars in Arthritis and Rheumatism, Journal Year: 2024, Volume and Issue: 69, P. 152562 - 152562

Published: Oct. 4, 2024

Language: Английский

Citations

1
Synergistic metabolic modulation of fibroblast-like synoviocytes via targeted dual prodrug nanoparticles to mitigate rheumatoid arthritis DOI Creative Commons
Shaobing Li, Jun‐Tao Lin, Chengxinqiao Wang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 15(1), P. 542 - 556

Published: Nov. 18, 2024

Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy inhibiting single target FLS using small molecular inhibitors limited for RA treatment. Herein, synergistic inhibition FLS' survival, proliferation, and activation by combining two inhibitors, diclofenac (DC) lonidamine (LND) was first verified. Subsequently, DC LND were individually conjugated to cystamine-modified hyaluronic acid (HA) prepare polymer-prodrug conjugates. A HAP-1 peptide-modified dual conjugates-assembled nanoparticles system (HAP-1NPDC+LND) further tailored optimal ratio targeted metabolic modulation alleviate symptoms. Upon uptake inflamed joints, HAP-1NPDC+LND released within intracellular reductive microenvironment, where hinders suppresses glycolytic enzymes eliminate synergistically. Additionally, secretion lactic pro-inflammatory factors from reduced, thereby disrupting crosstalk between macrophages. Finally, demonstrated promising mouse model collagen-induced (CIA). Overall, this research provides valuable insights into novel therapeutic strategies safe effective treatment through FLS.

Language: Английский

Citations

0