Curcumin’s niosomes coated with chitosan for the treatment of osteoarthritis: effect of cyclodextrin complexation

Curcumin represents a safer alternative to NSAIDs in osteoarthritis treatment due to its numerous favorable properties including anti-inflammatory and antioxidant power and limited side-effects. However, its scarce solubility/bioavailability requires powerful strategies to overcome these issues. In this work the effect of combining drug-cyclodextrin complexation, complex entrapment into niosomes, and chitosan-coating of niosomes to improve curcumin delivery by simultaneously exploiting the different benefits of such strategies, was investigated. With this aim, hydroxypropyl-βCyclodextrin (HPβCD) was selected as a complexing/solubilizing agent. Solid curcumin-HPβCD systems were prepared by different techniques and characterized, to select the best product. Niosomal formulations based on Span®60-Tween®60-cholesterol mixtures were developed and characterized for physicochemical properties. Chitosan-coating of the best formulation was optimized by experimental design. Finally, uncoated- and chitosan-coated-niosomes containing curcumin-HPβCD complex were prepared and compared to analogous vesicles loaded with the free drug. In vitro studies showed that curcumin entrapment into the vesicles as HPβCD complex rather than as free drug resulted in an increased and more prolonged release; moreover, chitosan-coating further contributed to this result and improved vesicle stability. In vivo studies on rats, performed by a monoiodoacetate model of osteoarthritis, confirmed the greater pain-relieving intensity and duration of the niosomal formulation containing the drug-HPβCD complex, and also highlighted the chitosan anti-inflammatory effect.