Actually if you read the next paragraph the explanation is quite clear.The article checked penetration of copper only, not of the whole compound.Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy
http://www.ncbi.nlm....les/PMC2945467/
That was what they were mainly interested in - delivering copper, not GHK.
It is possible that only the copper fraction dissociated from the GHK and penetrated. In fact, they acknowledge this explicitly. For example:In other words, they are saying the GHK may well have got left behind. They are certainly not testing for penetration of GHK at all.Such high tissue retention of copper may be attributed to intradermal decomplexation and re-binding to various endogenous amino acids of higher nucleophilic donor capacity than the original ligand.
Assessing whether permeant retained in skin tissues, the stratum corneum in particular, eventually becomes available systemically is an issue of ongoing discussions. Reservoir formation in the course of in vitro studies has been addressed [17]. Retained drug may be lost to natural desquamation, limiting its eventual systemic availability. On closer analysis, however, it has been found that the fraction of chemical sloughing off versus the part that becomes systemically available depends on the ratio of lag time to the turnover time for the stratum corneum [18]. Accordingly, at least 80% of the amount in the stratum corneum will become available if the lag time for penetration through that tissue is less than approximately 16 h This corresponds to 5% of the typical stratum corneum turnover time of 14 days. Consequently, based on our results where lag times ranged from 2 to 7 h, the copper retained in the stratum corneum has the potential to become systemically available also. As a result of the experiment with dermatomed skin, by topical application of GHK-Cu under the present conditions 200–250 μg/cm2 copper may become systemically available. Since the experiment was conducted ex vivo, it is possible that even larger amounts will be retained in the deeper dermal tissue in vivo, to be followed by further diffusion.
http://www.ncbi.nlm....les/PMC2945467/
They are talking about penetration the COPPER. They explicitly hypothesize that they think the copper is retained well because it gets dissociated from the GHK, suggesting that they think the GHK would hinder retention. It is unclear why they think this and where they think the GHK goes - but they didn't try to detect GHK, so we can really not conclude anything about GHK penetration from their experiment. For all we know the GHK is lysed in the first surface cell it enters after donating the copper. Or not. The experiment doesn't say.Such high tissue retention of copper may be attributed to intradermal decomplexation and re-binding to various endogenous amino acids of higher nucleophilic donor capacity than the original ligand.
Which makes perfect sense considering the purpose of the study:
Skin retention and penetration by copper applied as glycyl-l-histidyl-l-lysine cuprate diacetate was evaluated in vitro in order to assess its potential for its transdermal delivery as an anti-inflammatory agent.
So we're good here.