Pharmacological reports : PR · 2020
Ortho-vanillin nanoparticle-doped glucan microspheres exacerbate the anti-arthritic effects of methotrexate in adjuvant-induced arthritis in rats.
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Nasr Shiva, Varshosaz Jaleh, Hajhashemi Valiolah
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Co-administration of MTX and vanillin-doped GPs may be more effective than MTX alone in RA.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Co-administration of MTX and vanillin-doped GPs may be more effective than MTX alone in RA.