Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder with synovitis and articular pathology as its primary expositions. Leflunomide (Lfd) is an anti-rheumatic drug that is effective in the treatment of RA, but displays severe side effects upon prolonged systemic administration. Lo...
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/3/519 |
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| author | Ekta Singh Riyaz Ali M. Osmani Rinti Banerjee Amr Selim Abu Lila Afrasim Moin Khaled Almansour Hany H. Arab Hadil Faris Alotaibi El-Sayed Khafagy |
| author_facet | Ekta Singh Riyaz Ali M. Osmani Rinti Banerjee Amr Selim Abu Lila Afrasim Moin Khaled Almansour Hany H. Arab Hadil Faris Alotaibi El-Sayed Khafagy |
| author_sort | Ekta Singh |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder with synovitis and articular pathology as its primary expositions. Leflunomide (Lfd) is an anti-rheumatic drug that is effective in the treatment of RA, but displays severe side effects upon prolonged systemic administration. Local therapy might represent a promising strategy to treat rheumatoid arthritis without eliciting systemic adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) nanoparticles (Lfd-NPs) were prepared and assessed as a local drug delivery system capable of alleviating RA-associated inflammation. Lfd-NPs were optimized using the Quality by Design (QbD) approach, applying a 3<sup>2</sup> full factorial design. In vitro drug release from NPs was examined in simulated synovial fluid. In addition, the in vivo efficacy of Lfd-NPs was evaluated in the Adjuvant Induced Arthritis (AIA) rodent model. Sustained drug release in simulated synovial fluid was observed for up to 168 h. A gradual reduction in paw volume and knee diameter was observed over the course of treatment, indicating the regression of the disease. In addition, significant reductions in serum proinflammatory markers and cytokines, including the C-reactive protein (CRP), rheumatoid factor (RF), TNF-α, IL1-β, and IL-6, were verified upon treatment with Lfd-NPs, suggesting the modulation of immune responses at the pathological site. Most importantly, no remarkable signs of toxicity were observed in Lfd-NP-treated animals. Collectively, intra-articularly administered Lfd-NPs might represent a potential therapeutic alternative to systemically administered drugs for the treatment of rheumatoid arthritis, without eliciting systemic adverse effects. |
| first_indexed | 2024-03-09T12:59:34Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T12:59:34Z |
| publishDate | 2022-02-01 |
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| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2a669f746a5847c5a6910b8a06b878902023-11-30T21:56:02ZengMDPI AGPharmaceutics1999-49232022-02-0114351910.3390/pharmaceutics14030519Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent ModelEkta Singh0Riyaz Ali M. Osmani1Rinti Banerjee2Amr Selim Abu Lila3Afrasim Moin4Khaled Almansour5Hany H. Arab6Hadil Faris Alotaibi7El-Sayed Khafagy8Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, IndiaDepartment of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru 570015, IndiaDepartment of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, IndiaDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi ArabiaRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder with synovitis and articular pathology as its primary expositions. Leflunomide (Lfd) is an anti-rheumatic drug that is effective in the treatment of RA, but displays severe side effects upon prolonged systemic administration. Local therapy might represent a promising strategy to treat rheumatoid arthritis without eliciting systemic adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) nanoparticles (Lfd-NPs) were prepared and assessed as a local drug delivery system capable of alleviating RA-associated inflammation. Lfd-NPs were optimized using the Quality by Design (QbD) approach, applying a 3<sup>2</sup> full factorial design. In vitro drug release from NPs was examined in simulated synovial fluid. In addition, the in vivo efficacy of Lfd-NPs was evaluated in the Adjuvant Induced Arthritis (AIA) rodent model. Sustained drug release in simulated synovial fluid was observed for up to 168 h. A gradual reduction in paw volume and knee diameter was observed over the course of treatment, indicating the regression of the disease. In addition, significant reductions in serum proinflammatory markers and cytokines, including the C-reactive protein (CRP), rheumatoid factor (RF), TNF-α, IL1-β, and IL-6, were verified upon treatment with Lfd-NPs, suggesting the modulation of immune responses at the pathological site. Most importantly, no remarkable signs of toxicity were observed in Lfd-NP-treated animals. Collectively, intra-articularly administered Lfd-NPs might represent a potential therapeutic alternative to systemically administered drugs for the treatment of rheumatoid arthritis, without eliciting systemic adverse effects.https://www.mdpi.com/1999-4923/14/3/519drug deliverynanotherapeuticsrheumatoid arthritisleflunomidepolymeric nanoparticlepoly-ε-caprolactone |
| spellingShingle | Ekta Singh Riyaz Ali M. Osmani Rinti Banerjee Amr Selim Abu Lila Afrasim Moin Khaled Almansour Hany H. Arab Hadil Faris Alotaibi El-Sayed Khafagy Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model Pharmaceutics drug delivery nanotherapeutics rheumatoid arthritis leflunomide polymeric nanoparticle poly-ε-caprolactone |
| title | Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model |
| title_full | Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model |
| title_fullStr | Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model |
| title_full_unstemmed | Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model |
| title_short | Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model |
| title_sort | poly ε caprolactone nanoparticles for sustained intra articular immune modulation in adjuvant induced arthritis rodent model |
| topic | drug delivery nanotherapeutics rheumatoid arthritis leflunomide polymeric nanoparticle poly-ε-caprolactone |
| url | https://www.mdpi.com/1999-4923/14/3/519 |
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