Transdermal Delivery

Transdermal delivery means systemic absorption through intact skin, a different claim from topical application acting on the skin itself. The barrier is the stratum corneum, a layer of dead corneocytes in a lipid matrix that admits molecules only by a slow, tortuous diffusion path. Passive permeation is effectively restricted to compounds that are small, generally under about five hundred daltons, moderately lipophilic and potent enough to work at the tiny fluxes skin permits. Peptides fail all three tests at once.

The evidence bears this out: every approved passive transdermal patch is a small molecule, including nicotine, fentanyl, estradiol and scopolamine, and no peptide has reached approval as a passive patch. Active approaches breach the barrier physically. Microneedle arrays create transient micron-scale channels through the stratum corneum, with coated or dissolving tips carrying the drug; iontophoresis drives charged molecules with a small applied current. Both have yielded approved small-molecule products, but peptide programmes on these platforms have stalled short of approval.

The attraction is steady input without first-pass metabolism, reversible by removing the system; the limit is flux. Microneedle payloads are constrained by how much drug fits on or in the tips, which restricts the approach to potent compounds, and any active method adds a device, a use-error surface and a manufacturing burden the drug must justify.

The term is misused routinely in cosmetics, where peptide creams are marketed with transdermal language while at best acting within the epidermis. A related error assumes a home microneedling roller with a peptide serum reproduces a microneedle array: an array is a sterile, characterised drug product with a known delivered amount, while a roller is an uncharacterised breach of the barrier.