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Methotrexate (MTX) commonly used in rheumatoid arthritis (RA) has severe adverse effects. Ortho-vanillin, an inhibitor of Toll-like receptors (TLR), can prevent inflammation. Glucan is a cereal fiber recognized by dectin-1 or β-glucan receptors of phagocytic macrophages. The purpose of the current project was to study the effect of co-administration of MTX and vanillin by targeted delivery to macrophages using β-glucan microspheres to reduce inflammation of RA. MTX and vanillin nanoparticles in bovine serum albumin (BSA) or gelatin were doped in glucan particles (GPs) and characterized for their physical properties. Twenty-four hours after induction of RA in paw of rats, they received normal saline (1 mg/kg, ip), MTX (2 mg/kg/week, ip), β-glucan (1 mg/kg/week, ip), GPs-MTX (2 mg/kg/week, ip), GPs-vanillin (200 mg/kg/day, po), and GPs-MTX (2 mg/kg/week, ip) plus GPs-vanillin (200 mg/kg/day, po). The last group received free MTX ip and vanillin po for 14 days. Then, joint diameters, TNF-α and IL-6, were evaluated in rats. The particle size of the GPs was 5.3 µm. MTX loading efficiency in glucan microspheres was 64.5% and vanillin 44.2%. The microspheres released 88.7% of MTX and 95.1% of vanillin over 24 h. The results of in vivo studies showed a significant reduction in paw volume, TNF-α and IL-6 (p < 0.05) in animals treated with combination of MTX and vanillin-doped glucan microspheres compared to the mixture of the two drugs in free form or each drug alone. Co-administration of MTX and vanillin-doped GPs may be more effective than MTX alone in RA.


Shiva Nasr, Jaleh Varshosaz, Valiolah Hajhashemi. Ortho-vanillin nanoparticle-doped glucan microspheres exacerbate the anti-arthritic effects of methotrexate in adjuvant-induced arthritis in rats. Pharmacological reports : PR. 2020 Jun;72(3):680-691

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PMID: 32274768

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