Methotrexate nanoparticle delivery system for treatment of inflammatory bowel disease in pediatric patients

Purpose: To evaluate the efficacy and safety of methotrexate (MTX) nanoparticles in pediatric patients with inflammatory bowel disease (IBD). Methods: In this randomized, open-label clinical study, 28 pediatric patients with moderate to severe IBD were randomly assigned to treatment (MTX nanoparticles,15 mg/week) or control (azathioprine, AZA, 2 mg/kg/day) group. Nanoparticles were synthesized by adding calcium chloride to sodium alginate solution containing MTX, and was further treated with poly-L-lysine aqueous solution. The nanoparticles were evaluated for particle size, zeta potential and drug encapsulation efficacy. Erythrocyte sedimentation rate, C-reactive protein, aspartate aminotransferase, alanine transaminase, and disease activity scores were used to assess IBD remission. Results: Nanoparticle size, zeta potential and encapsulation efficacy were 164.4 ± 6.9 nm, -32.6 ± 3.7 mV, and 97.8 ± 4.2 %, respectively. After 12 weeks of therapy, the mean Pediatric Crohn\'s Disease Activity Index (PCDAI) scores for control and treatment groups were 22.3 ± 2.14 and 16.8 ± 1.87, respectively, while mean Pediatric Ulcerative Colitis Activity (PUCAI) Index scores were 24.3 ± 1.47 and 18.7 ± 1.92, respectively. Eight patients in the treatment and five patients in the control group achieved remission. Biochemical parameters varied significantly between the groups. Conclusion: MTX nanoparticles are safe and more effective than standard first-line IBD therapy. However, further studies are required to determine the suitability of the formulation for therapeutic use.

Effect of Arisaema erubescens (Wall) Schott rhizome extract on rheumatoid arthritis

Purpose: To investigate the anti-arthritic activity of the water extract of Rhizoma Arisaematis (WERA) using a collagen II -induced arthritis (CIA) rat model. Methods: CIA was induced in male Sprague-Dawley rats by intradermal injection of bovine collagen II in Complete Freund’s Adjuvant. The rats were treated with daily oral doses of WERA (100, 200, and 400 mg/kg) for 21 consecutive days. Methotrexate (MTX, 3 mg/kg), used as a positive control, was administered orally 2 times/week for 3 weeks. The severity of arthritis was evaluated using indices of paw swelling, arthritic score, body weight, thymus index, and spleen index. In addition, the serum levels of IL-1β, IL-6, IL-10, and TNF-α were measured. Results: All doses of WERA significantly inhibited paw edema (p < 0.01), decreased arthritis scores (p < 0.01) and spleen index (p < 0.05), and alleviated the weight loss associated with CIA in rats. Furthermore, TNF-α, IL-1β, and IL-6 serum levels were significantly decreased (p < 0.05) by all doses of WERA. By contrast, IL-10 serum levels were markedly increased (p < 0.05). Conclusion: WERA exerts therapeutic effects in CIA in rats by decreasing the serum levels of TNF-α, IL-1β, IL-6 and IL-10, suggesting WERA may be an effective candidate drug for treating human rheumatoid arthritis.

Ameliorative effect and potential mechanism of Ermiao san on adjuvant-induced arthritis in rats

Purpose: To investigate the effect and mechanism of action of Ermiao san (EMS), a traditional Chinese herbal formula, on inflammation development and production of inflammatory mediators in adjuvantinduced arthritis (AIA). Methods: AIA was induced by injection of 0.1 ml Freund’s complete adjuvant (FCA, 10 mg/ml) in the left hind footpad of the rats. AIA rats were intragastricly treated with 0.5, 1, 2 g/kg EMS or 0.1 g/kg methotrexate from day 7 to 28 after FCA challenge. Foot volume and histological score were measured. Osteoclast number was calculated by tartrate-resistant acid phosphatase (TRAP) staining assay. Levels of prostaglandin (PG) E2, tumor necrosis factor (TNF) -α and interleukin (IL)-1β in serum were determined by enzyme-linked immunosorbent assay (ELISA) while the level of nitric oxide (NO) in serum was analyzed by Griess reaction method. Results: Foot volume, histological score, osteoclast number and serum levels of TNF-α, IL-1β, PGE2 and NO were all increased in AIA group rats on day 28 after FCA challenge (all p < 0.01) compared with control. EMS (1 and 2 g/kg) significantly decreased the foot volume of AIA rats by 10 % (p < 0.05) and 19 % (p < 0.01), respectively, compared with AIA group. Furthermore, 1 and 2 g/kg EMS significantly reduced histological score by about 28 % (p < 0.05) and 46 % (p < 0.01), respectively, as well as osteoclast number by 12 % (p < 0.05) and 15 % (p < 0.05), respectively, compared with AIA group. In addition, 1 and 2 g/kg EMS significantly decreased the serum levels of TNF-α about 23 % (p < 0.05) and 43 % (p < 0.01), IL-1β by15 % (p < 0.05) and 26 % (p < 0.01), NO 13 % (p < 0.05) and 26 % (p < 0.01) as well as PGE2 by 11 % (p < 0.05) and 15 % (p < 0.01), respectively, compared with AIA group. Conclusion: These results suggest that EMS probably alleviates arthritis development and joint destruction by decreasing the production of inflammatory mediators in AIA rats.