The Potential Role of Topically Applied Heparan Sulfate in the Treatment of Photodamage

July 2015 | Volume 14 | Issue 7 | Original Article | 669 | Copyright © 2015

Richard L. Gallo MD PhD,a Vivian W. Bucay MD,b Ava T. Shamban MD,c Janice Lima-Maribona DO,d Amy B.
Lewis MD,e Cherie M. Ditre MD,f Flor A. Mayoral MD,g Michael H. Gold MDh

aDepartment of Dermatology, School of Medicine, University of California, San Diego, La Jolla, CA;
VA San Diego Healthcare System, San Diego, CA
bBucay Center for Dermatology and Aesthetics, San Antonio, TX
cAVA MD, Santa Monica, CA
dBay Pointe Dermatology & Cosmetics, Miami, FL
eAmy B. Lewis Dermatology, New York, NY
fPenn Dermatology, Penn Medicine Radnor, Radnor, PA
gMayoral Dermatology, Coral Gables, FL
hGold Skin Care Center, Nashville, TN

Abstract

Heparan sulfate is an essential glycosaminoglycan that plays important roles in development, homeostasis, and disease. As a group, the glycosaminoglycans provide mechanical strength to skin, as they can absorb water and occupy the space between elastin fibers and collagen. Heparan sulfate is also a key participant in cell proliferation, cell migration, collagen fiber formation, basement membrane regeneration, granulation tissue formation, and cell adhesion associated with wound healing. A variety of dermatological disorders are associated with changes in glycosaminoglycans or their associated proteoglycans. A new topical formulation of low molecular weight heparan sulfate glycosaminoglycan has been shown to penetrate the epidermis, basement membrane, and dermis within 24 hours of application. In an 8-week study, 15 patients using this new formulation showed improvement in skin hydration, skin firmness, skin elasticity, skin barrier function, and global fine lines and wrinkles. Incorporating low molecular weight heparan sulfate into topically applied formulations may represent a new approach to improving the appearance of photodamaged skin.

J Drugs Dermatol. 2015;14(7):669-674.

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INTRODUCTION

The advent of cosmeceuticals has revolutionized skin care. Dermatologists can now use topically applied compounds to address a variety of skin concerns with the goal of improving the signs of photodamage, such as uneven pigmentation, fine lines, tactile roughness, and skin tone. The benefits of both over-the-counter retinol and prescription retinoids such as retinoic acid (tretinoin) are well documented, as are the benefits of topical antioxidants such as vitamin C. Although certainly popular in cosmeceuticals, other agents such as peptides and growth factors have not been the subject of similar rigorous studies. Over the past several years, it has become apparent that cosmeceuticals can contribute to overall skin health by targeting certain issues that procedures cannot, namely oxidative stress and DNA repair. An extensively studied component of skin, heparan sulfate (HS), may be one of the most exciting and fascinating compounds that we now have available in the cosmetic arena. This report summarizes what we know about low molecular weight heparan sulfate (LMWHS) not only from a scientific perspective but also from initial clinical studies exploring its effectiveness on the skin.

In order to understand HS, we must first look at the skin and the building blocks that play a crucial role in skin health. These include the full spectrum of glycosaminoglycans (GAGs) besides HS, and molecules known as proteoglycans (PGs), which contain the GAG as a covalently attached side chain. PGs, with their ability to bind and alter enzymatic activity and protein-protein interactions, help to determine cellular responsiveness in development, homeostasis, and disease.1 PGs and GAGs are vital to life and have major roles in tissue remodeling, cell adhesion, growth factor responsiveness, and immune function.

Glycosaminoglycans and Proteoglycans

A GAG chain consists of repeating disaccharide pairs that usually include an acidic sugar alternating with a hexosamine. The acidic sugar may be iduronic acid or a glucuronic acid, and the hexosamine may be a glucosamine or galactosamine. GAG chains are linear and may contain up to several thousand disaccharides.2 Important GAGs and their paired disaccharide constituents in skin are shown in Table 1.

Except for hyaluronic acid, the GAGs in Table 1 are sulfated and covalently attached to core proteins. All must be enzymatically modified to become functional in skin. Dermatan sulfate (chondroitin sulfate B) is the major GAG in skin. Hyaluronic acid (hyaluran) in skin is neither sulfated nor covalently attached to a

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