Topical delivery of high molecular weight hyaluronic acid based on polysaccharide carrier and ultrasound application

Human skin aging is a complicated biological process, accompanied by many clinical signs such as loss of skin moisture,collagen degradation and wrinkles. The key molecule involved in delaying the aging process is hyaluronic acid (HA)‎,a glycosaminoglycan long linear polysaccharide. HA is one of the major elements in the extracellular matrix and due to its highly anionic properties, it can strongly bind water molecules to provide structural support and skin volume. HA highest concentrations is at the dermis, the lowermost layer of skin. Today,injections of high molecular weight (HMW) cross-linked HA are used to maintain skin hydration and for filling wrinkles. The main disadvantages of this treatment can range from mild symptoms such as localized pain or swelling to more serious problems such as severe injury due to injection into blood vessels in the skin. To overcome these disadvantages, we aim to develop a non-invasive delivery system of HMW HA for skin aging treatment. Delivering topically HMW HA to the target layer (dermis) can be challenging. The stratum corneum (SC),the outer layer of the skin, prevents penetration of large molecules (>500 Da).Also,naked HA has a relatively short half-life of less than a day in the skin due to enzymatic degradation. To overcome these obstacles, we evaluated the ability of ultrasound (US) application to increase the skin permeability and use a carrier for HA delivery to reduce its size through self-assembly for complexes formation. In this study,starch was synthesized and modified to positively charged carrier (Q-starch).The HA complexes were found to be ~100 nm in diameter and negatively charged spheres. In vitro skin permeability experiments were performed on porcine ear skins and the inter and transdermal delivery of fluorescently labelled HA complexes after US pre-treatment application were visualized using confocal microscopy. It was found that US succeeded to overcome the SC barrier of the skin,enhancing complexes penetration into the target dermis layer indicating on the potential of this protocol to improve the efficacy of the proposed treatment.