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Nanotechnology and Skin Delivery: Infinitely Small or Infinite Possibilities?
By: Johann W. Wiechers, PhD, JW Solutions
Posted: December 19, 2008, from the January 2009 issue of Cosmetics & Toiletries.
- Figure 1. Theoretical predictions of particle penetration
- Figure 2. Histological sections demonstrating the penetration depth
- Figure 3. Kinetics of the storage of nanoparticles
- Figure 4.The effect of particle size on the UV attenuating properties of titanium dioxide.
- Figure 5. Schematic representation of the size-dependent occlusive effect of lipid nanoparticles
- Figure 6: Cumulative amount of ketorolac
page 6 of 13
At a given depth, a higher percentage of hair follicles showed penetration of microspheres when the diameter was 0.75 and 1.5 µm than when their diameter was 3.0 and 6.0 µm, although these larger microparticles were still small enough to penetrate, in line with earlier findings.13 But even for the smallest microspheres tested, the maximum percentage of hair follicles showing penetration was only 60%, even at very superficial depths (less than 200 µm).16 This suggested that a large fraction of hair follicles do not show any skin penetration.
The reason why so many hair follicles do not show any skin penetration is that not all hair follicles are "available" for uptake of particles. The "availability" for transfollicular penetration depends on the conditions of application.17 If massage is applied during the application, the hair follicles open up and the skin penetration from particle-containing emulsions is statistically significantly enhanced (i.e., deeper). The average penetration is around 1500 µm relative to non-particle-containing emulsions where penetration averages around 500 µm. This is similar to what was shown in Figure 2, a picture that was also obtained following application with massage. When the same formulations were applied without massage, the average penetration was less deep and around 300 µm, irrespective of using particle-containing emulsions or non-particle-containing emulsions.17, 18
What is happening during massage? Massage actually opens a closed hair follicle. Follicles can be closed due to a cover of shed corneocytes that act as a plug. Follicles normally open due to sebum flow and hair growth, as demonstrated by the finding that dye penetrates whenever sebum secretion and/or hair growth is occurring.18 Investigations revealed that 74% of hair follicles on the upper forearm were open but that processes such as massaging and chemical peeling increased this percentage to 100%.19 Follicles can also be experimentally closed by blocking them with a nail varnish.20
The enhanced follicular penetration of nanomaterials via open follicles is speculated to be caused by the movement of the hair follicle (mimicked by massage) relative to the nanoparticle. Topically applied particles may be entrapped under the cuticular cells of the hair shaft and may be guided further down along the hair follicle duct as the hair moves back and forth. This concept of particle penetration into the hair follicles has recently been introduced by the Lademann group and termed the geared pump hypothesis.18
Experimental Data on Penetration to the Viable Epidermis
Theory dictates that particles do not penetrate to the viable epidermis, but what do the experiments show? Particles, especially the smaller ones, do penetrate into the infundibulum, although to pull them in, massage is required. Is this creating an exposure as described above, or do the nanoparticles merely constitute a reservoir without any further penetration into the living tissues, as suggested in Figure 3?