New Drugs Against Acne Vulgaris In The Light Of Paradigm Shift: From Bacteria to Inflammation Target

The paradigm of acne mechanism has shifted over time, from an emphasis on sebum production and overgrowth of bacteria C. acnes to an understanding of acne as an inflammatory skin disorder. The role of inflammation in the pathology of acne was reviewed by Dr. Tanghetti 1. The author concluded that emerging data indicates that acne vulgaris is a primary inflammatory disease, with histological, immunological, and clinical evidence suggesting that inflammation occurs at all stages of acne lesion development. Because inflammation is critical to all types of acne lesions and it is multifactorial, anti-inflammatory drugs are expected to exert significant effects against all lesion stages, albeit via distinct anti-inflammation mechanisms. Inflammation is a complex process that involves different types of innate immune cells. However, some cells could serve as a trigger. It was hypothesized that mast cells have a pleiotropic role in triggering inflammation in cutaneous diseases such as acne vulgaris, rosacea, chronic urticaria and others. A new paradigm of acne treatment is in the targeting the root of inflammation i.e. cells that trigger this process and support it via releasing of pro-inflammatory factors. There are two approaches to target mast cells: 1) to ablate all mast cells; 2) to calm them down via mast cell stabilizer that prevent degranulation process releasing pro-inflammatory cytokines. We explore a new approach and introduce first-in-class lipophilic mutual prodrug CromAzol™ that penetrate through upper protective layer of human skin (stratum corneum) and release two parent drugs in viable skin layers: effective and safe mast cell stabilizer sodium cromolyn and anti-bacterial, comedolytic and anti-inflammatory drug azelaic acid. Working together both drugs amplify their anti-inflammation properties thus provide the desired synergistic effect.