stilbenes and sorbitan-monostearate

Resveratrol and curcumin are two natural polyphenols extensively used due to their remarkable anti-inflammatory activity. The present work presents an inedited study of the in vivo antioedematogenic activity of these polyphenols co-encapsulated in lipid-core nanocapsules on Complete Freund's adjuvant (CFA)-induced arthritis in rats. Lipid-core nanocapsules were prepared by interfacial deposition of preformed polymer. Animals received a single subplantar injection of CFA in the right paw. Fourteen days after arthritis induction, they were treated with resveratrol, curcumin, or both in solution or loaded in lipid-core nanocapsules (1.75 mg/kg/twice daily, i.p.), for 8 days. At the doses used, the polyphenols in solution were not able to decrease paw oedema. However, nanoencapsulation improved the antioedematogenic activity of polyphenols at the same doses. In addition, the treatment with co-encapsulated polyphenols showed the most pronounced effects, where an inhibition of 37-55% was observed between day 16 and 22 after arthritis induction. This treatment minimized most of the histological changes observed, like fibrosis in synovial tissue, cartilage and bone loss. In addition, unlike conventionally arthritis treatment, resveratrol and curcumin co-encapsulated in lipid-core nanocapsules did not alter important hepatic biochemical markers (ALP, AST, and ALT). In conclusion, the strategy of co-encapsulating resveratrol and curcumin in lipid-core nanocapsules improves their efficacy as oedematogenic agents, with no evidence of hepatotoxic effects. This is a promising strategy for the development of new schemes for treatment of chronic inflammation diseases, like arthritis.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Curcumin; Drug Carriers; Foot Joints; Grape Seed Extract; Hexoses; Injections, Intraperitoneal; Male; Nanocapsules; Polyesters; Polysorbates; Rats, Wistar; Resveratrol; Stilbenes; Treatment Outcome

Polyphenols, which are secondary plant metabolites, gain increasing research interest due to their therapeutic potential. Among them, resveratrol and curcumin are two agents showing antioxidant, anti-inflammatory, antimicrobial as well as anticarcinogenic effects. In addition to their individual therapeutic effect, increased activity was reported upon co-delivery of the two compounds. However, due to the poor water solubility of resveratrol and curcumin, their clinical application is currently limited. In this context, lipid-core nanocapsules (LNC) composed of an oily core surrounded by a polymeric shell were introduced as drug carrier systems with the potential to overcome this obstacle. Furthermore, the encapsulation of polyphenols into LNC can increase their photostability. As the attributes of the polyphenols make them excellent candidates for skin treatment, the aim of this study was to investigate the effect of co-delivery of resveratrol and curcumin by LNC upon topical application on excised human skin. In contrast to the formulation with one polyphenol, resveratrol penetrated into deeper skin layers when the co-formulation was applied. Based on vibrational spectroscopy analysis, these effects are most likely due to interactions of curcumin and the stratum corneum, facilitating the skin absorption of the co-administered resveratrol. Furthermore, the interaction of LNC with primary human skin cells was analyzed encountering a cellular uptake within 24h potentially leading to intracellular effects of the polyphenols. Thus, the simultaneous delivery of resveratrol and curcumin by LNC provides an intelligent way for immediate and sustained polyphenol delivery for skin disease treatment.

Topics: Cell Survival; Cells, Cultured; Curcumin; Drug Carriers; Drug Liberation; Fibroblasts; Grape Seed Extract; Hexoses; Humans; In Vitro Techniques; Nanocapsules; Oils; Polyesters; Polyphenols; Resveratrol; Skin Absorption; Stilbenes