Commentary: Dermal formulations that deliver therapeutic drugs directly to the dermis, muscle, and mucosal tissues

Dermal formulations have traditionally been classified as either topical agents that relieve local symptoms (Dermal Formulation A) or as transdermal drug delivery systems designed to achieve systemic therapeutic effects (TDDS; Dermal Formulation B). Recently, a third category—Dermal Formulation C—has been proposed as having completely different dermato- and systemic-pharmacokinetic properties than dermal formulations A and B. Dermal Formulation C delivers drugs through the epidermis directly to subepidermal tissues such as the dermis, muscle, or knee joint, or to specific target organs such as the conjunctiva or trachea which are deeper tissues below cutaneous blood vessels, offering a novel therapeutic concept distinct from conventional topical and transdermal systems. This mini-review outlines the characteristics and therapeutic roles of these three categories. Dermal Formulation A treats local inflammation, itching, and infections caused by microbial invasion. Dermal Formulation B delivers drugs across the epidermis into systemic circulation to manage systemic diseases. In contrast, Dermal Formulation C is designed to transport drugs directly to subepidermal tissues while minimizing absorption into dermal blood vessels. Its pharmacokinetic profile involves both direct deliveries to target tissues and partial systemic distribution, enhancing pharmacological efficacy. Initially developed for inflamed or painful muscle tissues, Dermal Formulation C has recently been investigated for ocular drug delivery via eyelid skin to the conjunctiva, and for respiratory or allergic diseases through application to the cervical or nasal regions. This mini-review defines Dermal Formulation C, summarizes its development and pharmacokinetic features, and highlights its current applications and future potential. (245 words)