Curcumin and resveratrol loaded in nanostructured mesoporous silica as a promising delivery system in inflammatory bowel disease

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease that significantly impacts mortality and morbidity worldwide. Unfortunately, there is no current curative treatment for this condition. Consequently, it is important to explore alternative treatment approaches. Polyphenols like resveratrol (RSV) and curcumin (CUR) could be good treatment candidates, due their pharmacological properties, such as strong antioxidant and antiinflammatory activities. Despite their benefits, these compounds suffer from low solubility and intestinal permeability, resulting in their limited use in current therapies. In order to overcome the physico-chemical issues surrounding RSV and CUR, this work aims to encapsulate them in mesoporous silica particles (MS) as a strategy to improve their performances in the colitis treatment, using a mouse induced colitis model. The particles were in-house synthesised using tetraethyl orthosilicate (TEOS). RSV and CUR were successfully encapsulated separately into MS particles (drug loading 19 %). Mice were induced to UC using 3 % dextran sodium sulphate (DSS) added to the animals’ water. The animals were treated for 7 days with sulfasalazine (100 mg/kg), free polyphenols (40 mg/kg), MS-CUR and MS-RSV (200 mg/kg) and blank particles (200 mg/kg). At the end of the treatments the colons were measured and their homogenates submitted to cytokines evaluation and histological analysis. Encapsulation in MS showed partial amorphization of polyphenols, which contributed to an increase in their solubility. The encapsulated polyphenols maintained the colon length/weight ratio in the animals, unlike free polyphenols (p < 0.05). In the same way, they were able to reduce the interleukins IL-1β and IL-6 (p < 0.05). These findings indicate that MS particles loaded with RSV and CUR are suitable for treating UC by reducing local inflammation.