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The Four Rs of Skin Delivery
By: Johann W. Wiechers, PhD, JW Solutions
Posted: December 9, 2008
page 3 of 6
Microcapsules: Although microcapsules do provide a protective functionality, the main reason for their use as a skin delivery system is their controlled release characteristic, which will be discussed later in this article.
Delivering to the Right Site
The second of the four Rs looks at nanotechnology as a skin delivery system to ensure the right chemical is being delivered to the right site. Of the four Rs that can be affected in cosmetic skin delivery, ensuring the right chemical is being delivered to the right site is technically by far the most difficult one. Targeting can be created by either getting a system to accumulate in a specific subsection of the skin or—in case of an encapsulating system—by ensuring that the release of the content happens exclusively at the target site. The first mechanism depends on predominantly physical grounds such as size exclusion whereas the second mechanism relies on much more biochemical principles such as the presence of specific enzymes in cancerous tissue which—if the presence of such an enzyme triggers the release—allows a high tumor-to-normal tissue drug ratio.
In cosmetics, one is dealing with healthy skin and therefore the opportunities to use targeting via the biochemical route are very limited. This actually leaves only the physical route such as size exclusion and the only sites in the skin where this can be used are the holes in the skin: the sebaceous glands, the sweat glands and the infundibulum (the orifice around the hair follicle). This principle was already described in the mid-1990s by Rolland et al.8 who described that fluorescent particles with a diameter between 3 μm and 10 μm penetrated almost exclusively via the sebaceous glands and the transfollicular orifice, whereas particles smaller than 3 μm penetrated generally into the skin and those greater than 10 μm did not penetrate the stratum corneum at all (see Figure 1, modified from Reference 8).
More than 10 years passed before the next paper emerged. Ossadnik et al. described that particles in the range of 300 nm penetrated more efficiently into the orifice around the hair follicle than the same chemical solubilized in non-particle-containing emulsions,9 but this will be discussed more in detail in a future article (Part II) when dealing with particle penetration. Considering the size of these particles (typically below 100 nm), the use of such particles to improve skin delivery definitely belongs to the skin delivery applications of nanotechnology.
Delivering at the Right Concentration
The third of the four Rs examines nanotechnology as a skin delivery system to ensure the right chemical is being delivered to the right site at the right concentration. Many of the skin delivery systems or parts thereof contribute to the third R of delivery: to ensure that the Right concentration is being delivered. Penetration enhancers, liposomes, transfersomes, niosomes, ethosomes, volatile silicones, liquid crystals and emulsions (both emollients and emulsifiers) all play a role in achieving this Right concentration. They all have the capability to enhance skin penetration, but—as always—they can do this in different ways. According to the well-known Fick’s First Law of Diffusion, the flux, J, of a chemical through the skin equals to Equation 1 in which kp is the permeability coefficient, ΔC the concentration difference between the concentrations at the top and bottom of the stratum corneum, D the diffusion coefficient, K the partitioning coefficient and L the length of the pathway of diffusion. As long as we do not use microneedles (a future and upcoming cosmetic delivery system, described in the November 2008 Cosmetics & Toiletries magazine), there will be no change in L. This means that at the same loading of active ingredient in the formulation (ΔC), there will be only two possibilities for skin delivery systems to increase the input of chemicals into the stratum corneum: by increasing the D or by increasing the K.