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Targeting NF-κB and JAK/STAT pathways in rheumatoid arthritis: emerging nanocarrier-based drug delivery approaches

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Abstract

Rheumatoid arthritis (RA) is characterized by synovial inflammation, cartilage deterioration, and irreversible joint destruction, marking it as a chronic, progressive inflammatory disease. NF-κB and JAK/STAT are key molecular pathways that regulate inflammatory cytokine production, immune cell activation, and the persistence of inflammatory responses in RA. Conventional pharmacotherapies, including biologics and disease-modifying antirheumatic medications, are effective for treatment but face limitations like rapid clearance, systemic toxicity, poor absorption, and inadequate targeting of inflammatory areas. Recent advancements in nanocarrier-based drug delivery systems enhance tissue-specific targeting, improve pharmacokinetics, and enable controlled release, addressing existing limitations. This review demonstrates novel nanocarrier platforms aimed at modulating the NF-κB and JAK/STAT pathways, such as liposomes, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, and nanoemulsions. The effective encapsulation by these nanocarriers enhances the stability and therapeutic index of small-molecule inhibitors, nucleic acids (siRNA, miRNA), phytochemicals, and biologics. Stimuli-responsive systems aid controlled drug release triggered by oxidative stress, acidic pH, or enzymatic activity in RA joints, while surface-functionalized nanoparticles facilitate targeted delivery to inflamed synovium via ligand–receptor interactions. The combination of pathway-specific therapies and advanced nanocarrier technology holds promise for improving the care of RA by reducing systemic adverse effects, enhancing therapeutic precision, and improving patient outcomes. To enhance the effectiveness and commercial viability of RA treatments on these platforms, additional preclinical and clinical research is essential.

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Authors and Affiliations

  1. School of Pharmacy, ITM University, Turari Campus, Jhansi Road, Gwalior, Madhya Pradesh, India

    G. Surendra

  2. Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, 281406, India

    Jeetendra Kumar Gupta

  3. Department of Pharmacognosy, College of Pharmacy, Sri Venkateswaraa University, Chennai, Tamil Nadu, 600067, India

    E. Susithra

  4. Department of Pharmacology, Sri Venkateswaraa Medical College Hospital and Research Institute, Sri Venkateswaraa University, Chennai, Tamil Nadu, 600067, India

    A. C. Jesudoss Prabhakaran

  5. Department of Biochemistry, Sri Venkateswaraa Medical College Hospital and Research Institute, Sri Venkateswaraa University, Chennai, Tamil Nadu, 600067, India

    A. Jasmine Chandra

  6. Department of Pharmacy Practice, Sri Vijay Vijayalaya College of Pharmacy, Nallampalli, Dharmapuri, 636 701, India

    Vijayakumar Subash

  7. Department of Pharmaceutics, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Velan Nagar, Krishna Puram, Pallavaram, Chennai, Tamil Nadu, 600117, India

    Thukani Sathanantham Shanmugarajan & Uppuluri Varuna Naga Venkata Arjun

  8. Department of Pharmaceutical Analysis, Malla Reddy Institute of Pharmaceutical Sciences, Malla Reddy Vishwavidyapeeth (Deemed to be University), Secunderabad, Telangana, 500100, India

    Konatham Teja Kumar Reddy

  9. Department of Pharmaceutical Chemistry, Malla Reddy Institute of Pharmaceutical Sciences, Malla Reddy Vishwavidyapeeth (Deemed to be University), Secunderabad, Telangana, 500100, India

    Ramana Hechhu

Authors
  1. G. Surendra
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  2. Jeetendra Kumar Gupta
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  3. E. Susithra
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  4. A. C. Jesudoss Prabhakaran
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  5. A. Jasmine Chandra
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  6. Vijayakumar Subash
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  7. Thukani Sathanantham Shanmugarajan
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  8. Uppuluri Varuna Naga Venkata Arjun
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  9. Konatham Teja Kumar Reddy
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  10. Ramana Hechhu
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Contributions

G. Surendra: Conceptualization, methodology, investigation, data curation, and writing—original draft. Jeetendra Kumar Gupta: Methodology, investigation, and formal analysis. E. Susithra: Investigation and validation. A.C. Jesudoss Prabhakaran: Formal analysis, visualization, and writing—review and editing. A. Jasmine Chandra: Investigation and resources. Vijayakumar Subash: Methodology, software, and validation. Thukani Sathanantham Shanmugarajan: Formal analysis, supervision and writing—original draft. Uppuluri Varuna Naga Venkata Arjun: Data curation and visualization. Konatham Teja Kumar Reddy: Resources, validation and writing—original draft. Ramana Hechhu: Conceptualization, supervision, project administration, writing—review, editing and writing—original draft. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ramana Hechhu.

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Surendra, G., Gupta, J.K., Susithra, E. et al. Targeting NF-κB and JAK/STAT pathways in rheumatoid arthritis: emerging nanocarrier-based drug delivery approaches. Inflammopharmacol (2026). https://doi.org/10.1007/s10787-026-02203-8

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