The Skin Barrier: Why Peptides Face an Uphill Battle
Your skin isn't designed to absorb things easily. The outermost layer, called the stratum corneum, acts like a security system built to keep foreign molecules out. It's made of dead skin cells sandwiched between layers of lipids, and this structure does its job too well for peptide researchers.
Peptides typically range from 500 to 3000 daltons in molecular size. Transdermal delivery systems generally struggle with anything above 500 daltons, which means most therapeutic peptides start at a disadvantage before you even apply them.
When peptides attempt to pass through skin, they mostly try the intercellular route, weaving between skin cells, or the transcellular route, going through cells directly. There's also the follicular route through hair follicles, but it accounts for only a small portion of potential absorption.
Injectable peptides bypass this entire barrier. That's why injection remains the standard delivery method for peptides that need to reach systemic circulation. The route matters enormously for bioavailability.