'Improved Antioxidant Penetration': Letter to the Editor

Letter to the Editor
April 11, 2014
Re: Some problems with "...Improved Antioxidant Penetration" April C&T article

I am always interested in anything which improves penetration, so I was keen to read the above article. However, I hit a number of problems.

First, the idea that antioxidants are actually proven to provide benefits to skin seems to me to be strange—there are lots of indirect experiments that show they do things in vitro, which might plausibly improve skin, but I’m not aware that the causal chain has been proved. Indeed, there is lots of evidence in other contexts that antioxidants can do damage, for the simple reason that the human body has been optimised over millions of years to deal with free radicals and it is rather unlikely that a crude chemical intervention is going to do much good.

Second, it has been shown repeatedly that liposomes provide no mechanism for enhancing skin delivery. To the extent that they are nanoparticles we know that nanoparticles can’t/don’t penetrate. To quote from [a Materials Views paper]: “Recently, it became evident that, in most cases, conventional 'rigid' liposomes are of little or no value as carriers for transdermal drug delivery as they do not deeply penetrate skin, but rather remain confined to the upper layers of the stratum corneum.”

To the extent that they are a bunch of surfactant-like molecules, the evidence that surfactants (other than SLS) do anything to skin penetration is very limited and in my view, incompatible with the idea that they are acting like surfactants if they do. Of course liposomes offer a nice way of packaging difficult actives for formulations with sensorial and marketing appeal, but that’s not the essence of this article.

Third, in general, high dose (1g!) 12-hr studies in Franz cells are totally irrelevant to the real case of a finite dose (2 mg/cm²) on human skin where the water first evaporates, then a lot of the formula is lost to hair and clothes after a few hours. Franz cell experiments are also notorious for being open to damage of the skin during preparation and/or operation, so they have to be done very carefully to get good information.

Fourth, and most significantly, there is normally a “breakthrough” time of 30-60 min followed by a steady rise in accumulated dose. But Figure 4, which is of cumulative dose, shows an initial amount (presumably the first measured point, so we actually have no idea of the actual time) followed by no further increase up to 12 hr. This seems to me to be more likely to be caused by some problem at t=0 than to real permeation of an unknown molecules (or molecules) from a liposome formula where those molecules might be safely wrapped inside the liposome unable to go anywhere. The fact that the non-liposome result shows less permeation is not relevant. As with so much of liposome work, the control formulation isn’t a genuine control because it is comparing with and without liposomes not with liposomes and the equivalent amount of lipid in non-liposome mode. In any event, the factor of 1.3 improvement is likely to be insignificant in any real application.

In summary, I believe that the logic of the paper is flawed in at least four ways. Unfortunately, there is a tendency in cosmetics to base subsequent claims on such papers (I’m not saying that that is the case here). The only claims that would really stand up are, if it was proven: (a) that the active went into the skin of a real human and (b) the active (rather than the generally nice formulation) improved the skin in some relevant manner. Of course if (a) is the case, then there is the further issue of proving safety, perhaps to pharmaceutical standards, of this unspecified extract. The fact that the extract is “natural” is not proof that it is safe, nor is the fact that it is an “antioxidant” proof that it doesn’t do any harm, as there are now well-documented cases of antioxidants (in other pharma conditions) disturbing the careful balance that nature had created over millions of years.

Professor Steven Abbott
Steven Abbott TNCF Ltd., UK

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