Nanotechnology and Skin Delivery: Infinitely Small or Infinite Possibilities?

Jan 1, 2009 | Contact Author | By: Johann W. Wiechers, PhD, JW Solutions
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Title: Nanotechnology and Skin Delivery: Infinitely Small or Infinite Possibilities?
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Once the reader accepts a standard definition of nanotechnology, such as that offered by The Royal Society and The Royal Academy of Engineering,1 and then reads my definition of skin delivery available elsewhere (see Two Definitions),2,3 and then realizes that micro- and nanoparticles accumulate in the furrows and ridges on the skin surface where they act as a reservoir, then they are ready to ask the question answered in this article: Do nano-particles penetrate human skin?

Nanoparticles have been defined as single particles with a diameter less than 100 nm,4 which includes titanium dioxide in transparent, inorganic sun care products, and is usually extended to 200 nm to include the zinc oxide in those products. But nanoparticles are only a subset of nanomaterials, which can also include cyclodextrins and liposomes. While cyclodextrins do not represent a nanotechnology in this author's opinion, liposomes do. However, liposomes will not be discussed in this article because unlike nanoparticles that are intended to rest on the skin, liposomes were specifically designed to penetrate the skin. Thus, the nanoparticles addressed in this article are solid particles with a diameter less than 200 nm.

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Figure 1. Theoretical predictions of particle penetration

Figure 1. Theoretical predictions of particle penetration
Figure 1. Theoretical predictions of particle penetration as performed by Michael S. Roberts, School of Medicine, University of Queensland, Princess Alexandra Hospital, Australia. (Reproduced with the author’s permission from Reference 10).

Figure 2. Histological sections demonstrating the penetration depth

Figure 2. Histological sections demonstrating the penetration depth
Figure 2. Histological sections demonstrating the penetration depth of particle-containing emulsions and non-particle-containing emulsions in the hair follicles of pig ear skin (laser scanning microscopy measurements). Left a): particle-containing emulsion; right b): non-particle-containing emulsion. (Taken with permission from Reference 14.)

Figure 3. Kinetics of the storage of nanoparticles

Figure 3. Kinetics of the storage of nanoparticles
Figure 3. Kinetics of the storage of nanoparticles a) in the hair follicles and b) in the stratum corneum. (Taken from Reference 15.)

Figure 4.The effect of particle size on the UV attenuating properties of titanium dioxide.

Figure 4.The effect of particle size on the UV attenuating properties of titanium dioxide.
Figure 4. The effect of particle size on the UV attenuating properties of titanium dioxide. Reduction of particle size moves the peak of UV attenuation to shorter wavelengths and also improves the transparency. However, the SPF efficacy is considerably reduced when the particle size is too small. The smallest particles (about 20 nm) do not exhibit real UV-protective benefits any longer, not even in the UVB, but such particles are still larger than the size of the quantum dots that were shown to penetrate pig26 and rat skin.27 (Modified from Reference 29.)

Figure 5. Schematic representation of the size-dependent occlusive effect of lipid nanoparticles

Figure 5. Schematic representation of the size-dependent occlusive effect of lipid nanoparticles
Figure 5. Schematic representation of the size-dependent occlusive effect of lipid nanoparticles; a) an aqueous dispersion of either solid lipid nanoparticles or nanostructured lipid carrier (diameter 500 nm), in comparison with b) a solid lipid microparticle dispersion (diameter 1 µm). (Reproduced with permission from Reference 34.)

Figure 6: Cumulative amount of ketorolac

Figure 6: Cumulative amount of ketorolac
Figure 6. The cumulative amount of ketorolac as a function of time from elastic and rigid vesicle formulations across human skin in vitro. Elastic vesicles were clearly more effective in the enhancement of ketorolac transport across the skin. (Reproduced with permission from Reference 37.)

Two Definitions

Two Definitions

Nanotechnology is defined as the design, characterization, production and application of structures, devices and systems by controlling shape and size at the nano-scale.1

Skin delivery means to transport the right chemical to the right site in the skin at the right concentration for the correct period of time.2,3

Some Perspective on 10-18 nmol/mL

1 x 10-18 nmole/mL is tiny. There are per mole 6.25 x 1023 molecules. 10-18 nmol/mL = 10-18 x 10-9 = 10-27 mole/mL = 10-27 x 6.25 x 1023 molecules/mL = 6.25 x 10-4 molecules/mL = 0.625 molecules/L. For a human being of 80 kg (roughly 80 liters), this means a skin penetration of 0.625 x 80 = 50 molecules per square centimeter in a normal human body.

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