Influence of low frequency ultrasound (LFU) associated with different coupling medium in skin permeability and topical skin cancer treatment.

Abstract

The application of low frequency ultrasound (LFS) to increase drug penetration into or through the skin is explored jus 16 yers. Many studies are required to understand the application of LFS in the permeation of macromolecules and drug delivery systems. It was recently demonstrated that the application of LFS leads to the formation of discrete regions in the skin, highly permeable and disorganized, known as "localized transport regions" (LTRs). There is evidence that the increase in molecules transport by LFS occurs due to the formation of these regions, which appear on the skin. However, formation of this regions are heterogeneous. As the formation of LTRs is correlated with cavitation process caused by LFS, it is estimated that changes in the coupling medium which can modify the cavitational parameters are able to lead to the formation of LTRs more evenly distributed on the skin surface . The greater control in the formation of LTRs, as well as possible changes in the characteristics of these pathways created in skin , it may be advantageous for the topical treatment of skin diseases such as skin cancer. Pretreatment of the skin with LFU, followed by application of solid lipid nanoparticles (SLN), which are a carrier of the antineoplastic doxorubicin (DOX) should increase DOX penetration to the deeper layers of skin, allowing the drug to be released in high concentrations in the layers of the skin where the skin tumors are located. Therefore, this project has two main objectives: to evaluate the influence of change in coupling medium composition in LTRs formation after LFS application on the skin, and to evaluate the influence of LFS on skin penetration of SLN containing DOX and its potential use in the topical treatment of skin cancer.Importantly, this project will start a new line of research related to the use of ultrasound as physical method to improve skin penetration of macromolecules and drug delivery systems. This new line will be implemented due to the post-doctoral stage recently completed by the coordinator of this project at MIT (USA), with FAPESP grant (Proc. 09 / 06150-9). The project has the support of Profs. Robert Langer and Daniel Blankschtein, both from MIT.