Stratum Corneum
The outermost layer of the skin, composed of dead keratinocytes (corneocytes) embedded in a lipid matrix. The stratum corneum is the primary barrier against environmental damage and transdermal drug absorption. Penetrating this barrier is the main challenge for topical and transdermal peptide delivery.
Technical Context
The stratum corneum (SC) follows the 'bricks and mortar' model: corneocytes (flattened, keratin-filled dead cells — the bricks) embedded in a lamellar lipid matrix (ceramides, cholesterol, free fatty acids in a 1:1:1 molar ratio — the mortar). SC thickness varies: approximately 10-15 cell layers (10-20μm) on most body sites, up to 100+ layers on palms and soles. The SC provides: barrier function (preventing transepidermal water loss — normal TEWL is 5-10 g/m²/h; values >25 indicate barrier disruption), UV protection (absorbing/scattering UV radiation), chemical resistance (preventing penetration of most exogenous substances), and microbial defence (acidic pH 4.5-5.5 and antimicrobial peptides create an inhospitable environment for pathogens). The SC is the primary barrier to transdermal peptide delivery — its lipophilic, tightly packed structure excludes large hydrophilic molecules like peptides, necessitating technologies like microneedles or iontophoresis for transdermal peptide delivery.