The Four Rs of Skin Delivery

By: Johann W. Wiechers, PhD, JW Solutions

Posted: December 9, 2008

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To prolong the time of delivery, a plethora of controlled release systems has been invented, which is, in my opinion, predominantly marketing hype because in most cases the skin delivery of an active ingredient needs to be enhanced in order to result in a clinical effect. If the effect is insufficient because insufficient material reaches the site of action to lift the levels of the active above the minimal effective concentration, controlled release is not going to help to increase these levels. Worse, the use of such systems controls the amount of active that reaches the skin to penetrate and compared to no system, it can only go down! Of course, there are some very specific cases where skin penetration might be too quick, or when an activity is only needed under specific conditions (e.g., release of a sweat-controlling active only when you sweat), but it would be better to call such systems "triggered release" or if you really want ,"controlled triggered release" systems. When someone offers you a controlled release system to be used in cosmetics, ask yourself the question whether the speed of active getting into the skin is really the problem with your application.

Technologically, the answer to controlled release in skin delivery is a particulate system like a microparticle or a nanoparticle that often combines stability and release characteristics. Almost without exception they belong to applications of nanotechnology. Particles can be either filled (solid) or open (hollow). A solid core provides more flexibility in controlling release (slower degradation) and has advantages for the stability of the active ingredient (see Figure 2).

When dealing with solid particles, two types can be differentiated: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). Because the names are rather non-descriptive (both are solid, both contain lipids, both are nanostructured and both are carriers), it takes quite a while to understand the real difference but Souto and Müller explain it very well in Reference 16. The difference between SLNs and NLCs is in the composition of the lipid matrix. The matrix consists of highly pure lipids for SLNs and a mixture of solid and liquid lipids for NLCs. The pure, solid lipids of the SLNs with their relatively perfect lipid crystals provide only little space where solubilized molecules can be inserted into the lipid crystal structure; SLN’s therefore have a limited loading capability. NLCs, on the other hand, are a mixture of solid and liquid lipids which yields crystal structures with many imperfections; NLCs therefore have a high loading capability. The typical particle size of such colloidal carriers is below 1 μm; that is at the high end of nanotechnology that typically deals with sizes from 20 to 200 nm, in particular from 20 to 100 nm.

The variety in these skin delivery systems comes from their release mechanisms, which can involve fracture, passive diffusion, fusion, enzymatic degradation and pH.¹⁷ When studying the scientific literature it quickly becomes apparent that the majority of papers describing these systems deal with either the stability of the encapsulated chemically labile molecule¹⁸ or the release and release mechanism of encapsulated molecules or both,¹⁹ whereas reports on enhanced skin delivery (i.e., larger amounts being delivered into skin) from micro- and nanoparticles are difficult to find. This suggests that these particles are used almost exclusively to enhance the stability of chemically labile molecules (the first R) and/or to optimize the time profile of skin delivery (the fourth R). But there is something else going on with micro- and nanoparticles. They accumulate in furrows and ridges on the skin surface where they act as a reservoir, and that leads to a discussion of whether particles and in particular nanoparticles can penetrate skin! That is the topic in Part II, appearing in the January 2009 issue of Cosmetics & Toiletries magazine.

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