Immunolipossomes for skin diseases application: influence of physical penetration enhancement methods

Abstract

The squamous cell carcinoma (SCC) holds the second position in frequency and is biologically more aggressive than the basocellular skin cancer. SCC over-expresses the epidermal growth factor receptor (EGFR), which is responsible for communicating extracellular signals to the nucleus and is commonly associated with bad prognosis. The interruption of the signaling pathway by the administration of cetuximab, a monoclonal antibody, is a current strategy to inhibit tumor growth. The topical chemotherapy of these tumors is a promising strategy for the reduction of the side effects associated to this kind of therapy. However, to reach the SCC, the drug needs to overcome the primary skin barrier, the stratum comeum (SC). The use of physical methods, such as iontophoresis and low frequency ultrasound (LFS), is then necessary to disturb the SC and permits the cetuximab to reach the tumor cells in high concentrations. Furthermore, the antibody activity is confonmation dependent, which means that aggregation changes cetuximab interactions with EGFR. Therefore, topical administration of cetuximab likely requires a delivery system. In this context, the aim of this work is to study different strategies, such as LFS, iontophoresis and drug delivery systems, to topically deliver cetuximab for skin SCC treatment. Liposomes encapsulated or covalently bound to cetuximab will be developed. The influence of LFS and iontophoresis in the tumoral penetration of the drug will be assessed and the efficacy of the drug delivery systems developed will be investigated in vivo. (AU)