Increasing Permeability of the Q-starch/miRNA Nano-complexes through the Skin by Multiple Ultrasound Exposures

In recent years it has been proposed to treat skin diseases, such as psoriasis, where there is an over-expression of specific proteins related to the development of the disease with microRNAs, a small RNA sequence (miRNA) that can silence expression of specific proteins in the cell.

Although it holds great potential, miRNA topical delivery is highly challenging due to three main obstacles: 1.miRNA molecule is unstable due to enzymatic degradation. 2. The inherent barrier properties of the top layer of the skin. 3. Both, miRNA and cell membrane are negatively charged , what cause electrostatic rejection between them. To overcome these obstacles, we use cationic modified Q-starch as carrier for miRNA molecule, and ultrasound for increasing skin permeability. Previous results from our laboratory confirmed the ability of one ultrasound application to insert nano-complexes of Q-starch/miRNA through skin layers, but many of them were accumulated in the upper layer of the skin. Based on these results, the hypothesis of the current research is that repeated ultrasound exposure will improve the ability to uniformly spread the nano-complexes in all skin layers (enhancing the convective transport and/or temporary modification of the skin structure) and thereby increase the disease healing potential.

Q-starch was synthesized and characterized by elementary analysis and FTIR. Q-starch/miRNA nano-complexes were prepared in a self-assembly formation and analyzed using and NanoSight. Skin permeability experiments were implemented on pig`s skin in diffusion cells, using fluorescently labeled nano-complexes. Ultrasound applications on the skin were performed before the nano-complexes were placed and 3 hours after the first application. The skin was scanned using confocal microscope. Additional ultrasound application was able to introduce more nano-complexes into the lower skin layers and spread them in a homogeneous manner, indicating the potential of this protocol to improve the efficacy proposed treatment.