Influence of low frequency sonophoresis on skin penetration of nanoparticles aiming the skin cancer treatment

Abstract

The application of low frequency sonophoresis (LFS) to increase the penetration of drugs into or through the skin has been studying for only 16 years. Many studies are still needed to understand and therefore tailor the application of LFS in the permeation of macromolecules and drug delivery systems. It was recently demonstrated that application of LFS leads to the formation of distinct regions in the skin, highly permeable and disorganized, known as localized transport regions (LTRs). There is evidence that the increased transport of molecules by LFS occurs due to formation of these regions, which appear on the skin, however, quite heterogeneous. As the formation of LTRs is correlated with the process of cavitation caused by LFS, it is estimated that the addition of substances such as nanoparticles, which control the nucleation sites of cavitation is able to lead the formation of LTRs more evenly distributed in the skin. The greater control on the formation of LTRs, as well as possible changes in the characteristics of these paths created in the skin, may be advantageous for the topical treatment of skin conditions such as skin cancer. Pretreatment of skin with the LFS, followed by application of solid lipid nanoparticles (SLN) loading the antineoplastic doxorubicin (DOX) may increase the skin penetration of the SLN to deep skin layers, allowing drug release from these particles, in high concentrations, in these layers of skin where the skin tumors are found. Therefore, this project has two main goals: to evaluate the influence of SLN added to the coupling medium in the formation of LTRs after LFS application on the skin, and to evaluate the effect of LFS on skin penetration of SLN containing DOX and its potential use in the topical treatment of skin cancer. Importantly, this project will initiate a new line of research on the use of ultrasound as a physical method to improve skin penetration of macromolecules and delivery systems. This new research line will be implemented through the stage of a post-doctoral recently finalized by the project coordinator at MIT (USA), with a FAPESP (Proc. 09/06150-9) grant. The project has the support of the post-doctoral supervisors, Prof. Robert Langer and Daniel Blankschtein, both from MIT. (AU)