Pharmaceutics (Nov 2020)

pH-Responsive Nanostructures Based on Surface Active Fatty Acid-Protic Ionic Liquids for Imiquimod Delivery in Skin Cancer Topical Therapy

  • Silvia Tampucci,
  • Lorenzo Guazzelli,
  • Susi Burgalassi,
  • Sara Carpi,
  • Patrizia Chetoni,
  • Andrea Mezzetta,
  • Paola Nieri,
  • Beatrice Polini,
  • Christian Silvio Pomelli,
  • Eleonora Terreni,
  • Daniela Monti

DOI
https://doi.org/10.3390/pharmaceutics12111078
Journal volume & issue
Vol. 12, no. 11
p. 1078

Abstract

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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.

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