Glycogen Synthase Kinase 3β Inhibitor Delivered by Chitosan Nanocapsules Promotes Safe, Fast, and Efficient Activation of Wnt Signaling In Vivo

The Wnt-β-catenin signaling is an evolutionarily conserved pathway with a prominent role in different biological processes such as stem cell renewal, cell proliferation, and differentiation. Wnt signaling dysfunctions have been associated with developmental and neurological diseases as well as formation and progression of tumors. Nanomedicine may provide safe and efficient drug delivery systems offering breakthrough innovation in targeting Wnt signaling. The natural polymer chitosan represents an excellent candidate for delivery platforms, showing interesting biophysical properties such as high biocompatibility and mucoadhesive properties. In this study, oily core chitosan nanocapsules were designed with the aim to deliver the Wnt signaling agonist alsterpaullone in the model organism Hydra vulgaris. Chitosan nanocapsules show negligible impact on animal morphology, without affecting the viability. Nile red-loaded nanocapsules reveal fast and efficient intracellular delivery of the fluorescent cargo. Short incubations with alsterpaullone-loaded nanocapsules ensure a more effective activation of Wnt signaling with respect to the same concentrations of the free drug. Altogether, these data provide evidence that chitosan nanocapsules may represent a very promising strategy for future therapies targeting the diseases associated with canonical Wnt signaling.