The outermost layer of skin, the stratum corneum, is a barrier built to keep large molecules out. It admits small, fat-soluble compounds and largely excludes large, water-soluble ones. Proteins fall in the excluded category. They are big, they are hydrophilic, and they degrade easily, which is why most proteins applied to the surface of the skin do not reach the living tissue beneath it.
This is the central obstacle for any growth-factor approach. The signaling that governs the follicle takes place in the dermis and at the base of the follicle, well below the stratum corneum. A growth factor that stops at the surface, or that breaks down before it arrives, does not reach the cells it would signal. Stability and depth of delivery are therefore the two properties that decide whether a topical protein can act at all.
Core Biogenesis has reported on this directly. In its skin explant studies, oleosome-bound protein was measured reaching the dermis, while the same protein applied without the oleosome carrier stayed in the epidermis. The company has also reported that the oleosome fusion stabilises protein structure by roughly eight to ten times relative to the unbound protein.
Depth and stability are the criteria any topical protein has to meet. The mechanism the program uses to meet them is the subject of Note 05.