Percutaneous Absorption
Percutaneous absorption is the passage of a substance through the stratum corneum and viable epidermis into the dermal microcirculation, and it is the rate limit on every topical active.
Absorption through skin is passive diffusion, described adequately by Fick's first law: flux equals a permeability coefficient multiplied by the concentration difference across the barrier. That coefficient collapses three things into one number, how well the molecule partitions into stratum corneum lipid, how fast it diffuses once there, and how long the path is. Most molecules take the tortuous intercellular route between corneocytes; follicles and sweat ducts offer a shortcut but occupy about a tenth of a percent of skin surface.
The physicochemical envelope is narrow. Passive permeation favours molecules under about five hundred daltons with an octanol-water log P in the low single digits and few hydrogen-bond donors; charged, hydrophilic species above a thousand daltons are essentially excluded. Site matters as much as chemistry, with classic hydrocortisone work showing absorption differing by more than an order of magnitude between forearm and scrotal skin.
Regulatory measurement uses in-vitro diffusion cells on excised human skin with full mass balance, and that accounting is the point: it separates material left on the surface, material lodged in the stratum corneum, and material that reached the receptor fluid and would in life have reached blood. Only the third is absorption, and for a peptide meant to act on dermal fibroblasts it is the only number that speaks to the claim.
The everyday error is accepting reservoir data as delivery data. Tape stripping recovers peptide from the outer dead layers and is regularly reported as penetration; confocal images of a fluorescently tagged peptide may be showing the tag once the two separate. Claims of dermal delivery derived from rodent skin, thinner and more densely follicular than human skin, overstate what happens on a face.