Introduction: Due to the well-organized structure and barrier function of the skin, it is generally difficult for drugs applied directly on the surface of skin to reach their expected site of action. Accordingly, site-specific drug delivery in the skin has been increasingly explored to facilitate the treatment of skin diseases and reduce the systemic toxicity. Area covered: An overview of the generally used sites for drug delivery in the skin is herein presented. Different strategies including particle-based carriers, physical technologies, and chemical approaches are discussed with regards to their potential application in site-specific drug delivery in the skin. Expert opinion: Particle-based carriers are of particular significance for the enhancement of drug delivery in the skin. Although no recommendation can be made regarding which type of carriers can provide better skin penetration, the lipid-based colloidal systems appear to be favored due to their compatibility. In addition, the physical technologies provide unique advantages in delivering hydrophilic macromolecules for the skin immunization. As a new class of permeation enhancers, skin penetrating peptides are gaining more attention in drug delivery to skin cells. For the design of robust site-specific drug delivery systems, the impacts of diseased state and drug properties should not be disregarded.
Keywords: Site-specific; drug delivery; microneedles; nanoparticles; prodrugs; skin disease.