Rutin-containing cyclodextrin nanosystems: a possible strategy for dietary supplementation in diabetics

The flavonoid rutin is an active ingredient with multiple health benefits featuring antioxidant, anti-inflammatory, cardiovascular, neuroprotective, anti-diabetic and anti-tumor activity, unfortunately characterized by physico-chemical instability and poor solubility in aqueous environment. The present study investigates the use of nanosystems for the delivery of rutin through oral administration for a possible dietary supplementation. In this view, rutin-containing cyclodextrins and rutin-in-cyclodextrin-in-liposomes (R-CL) have been studied. R-CL, obtained by the “thin film hydration” method, were initially homogeneous in size, but increased in the average diameter over time. R-CL showed greater encapsulation efficiency and stability of rutin over time compared to cyclodextrin complexes. R-CL were stable in term of rutin content and physically within 30 days of storage in a cool environment, showing no phase separation phenomena. The dialysis study through a Wistar rat small intestine fragment, demonstrated an increasing release of rutin from R-CL, reaching the plateau around the sixth hour. The use of a gastrointestinal fluid simulator within the selected biological fragment, led to a more linear and gradual release profile over time, still obtaining a complete release of the drug around the sixth hour. The in vitro experiments on HepG2 cells evidenced no cytotoxic effect for both R-CL and cyclodextrin-complex and a strong and significant increase in glucose uptake levels promoted by R-CL with respect to untreated cells, as well as to the other formulations. The data suggest that the formulation strategy based on the vesicular cyclodextrin system improves the biological effect of rutin on cells. However, further studies will be necessary to confirm the activity of rutin as food supplementation. • Rutin possesses interesting dietary characteristics • The widespread industrial food use of rutin as oral assumption is limited by its low water solubility • Simple and combined system between liposomes and cyclodextrins have been investigated to allow oral administration of rutin • In vitro studies suggest the interest as dietary supplementation in pathologies characterized by high blood glucose levels