For topical treatment of
skin cancer, the design of pH-responsive nanocarriers able to selectively release the drug in the
tumor acidic microenvironment represents a reliable option for targeted delivery. In this context, a series of newly synthesized surface-active
fatty acid-protic
ionic liquids (FA-PILs), based on tetramethylguanidinium
cation and different natural hydrophobic
fatty acid carboxylates, have been investigated with the aim of developing a pH-sensitive nanostructured drug delivery system for
cutaneous administration in the
skin cancer therapy. The capability of FA-PILs to arrange in
micelles when combined with each other and with the non-ionic
surfactant d-α-
Tocopherol polyethylene glycol succinate (
vitamin E TPGS) as well as their ability to solubilize
imiquimod, an immuno-stimulant drug used for the treatment of skin cancerous lesions, have been demonstrated. The FA-PILs-
TPGS mixed
micelles showed pH-sensitivity, suggesting that the acidic environment of
cancer cells can trigger nanostructures' swelling and collapse with consequent rapid release of
imiquimod and drug cytotoxic potential enhancement. The in vitro permeation/penetration study showed that the micellar formulation produced effective
imiquimod concentrations into the skin exposed to
acid environment, representing a potential efficacious and selective drug delivery system able to trigger the drug release in the
tumor tissues, at lower and less irritating drug concentrations.