More than skin deep: using polymers to facilitate topical delivery of nitric oxide

Skin, the largest organ in the human body, provides several important functions, including providing protection from mechanical impacts, micro-organisms, radiation and chemicals; regulation of body temperature; the sensations of touch and temperature; and the synthesis of several substances including vitamin D, melanin, and keratin. Common dermatological disorders (CDDs) include inflammatory or immune-mediated skin diseases, skin infection, skin cancer, and wounds. In the treatment of skin disorders, topical administration has advantages over other routes of administration, and polymers are widely used as vehicles to facilitate the delivery of topical therapeutic agents, serving as matrices to keep therapeutic agents in contact with the skin. Nitric oxide (NO), a cellular signalling molecule, has attracted significant interest in treating a broad spectrum of diseases, including various skin disorders. However, there are a number of challenges in effectively delivering NO. It must be delivered in a controlled manner at sufficient concentrations to be efficacious and the delivery system must be stable during storage. The use of polymer-based systems to deliver NO topically can be an effective strategy to overcome these challenges. There are three main approaches for incorporating NO with polymers in topical delivery systems: (i) physical incorporation of NO donors into polymer bases; (ii) covalent attachment of NO donors to polymers; and (iii) encapsulation of NO donors in polymer-based particles. The latter two approaches provide the greatest control over NO release and have been used by numerous researchers in treating CDDs, including chronic wounds and skin cancer.