User:Billiam1239/Sandbox

Permeability
Human skin permeability is the ability of foreign substances to penetrate and diffuse through the skin. Skin naturally has a low permeability, thus protects the body from particles and foreign toxins by not allowing them to penetrate through the surface. However, technologies in nanomedicine and biology have led to developments in techniques to increase permeability of skin for various applications. The stratum corneum is the outermost layer of skin and is an effective barrier to most inorganic nanosized particles. Nanomedicine researchers are interested in nanoparticles that can penetrate the stratum corneum and settle in the epidermis where cells primarily reproduce. If the nanoparticles are targeted to surround cancer cells, they can be used to map where the cancer is located and deliver therapeutic agents directly to the site.

Nanoparticles
Nanoparticles 40nm in diameter and smaller have been successful in penetrating the skin. Research confirms that nanoparticles larger than 40nm do not penetrate the skin past the stratum corneum. Most particles that do penetrate will diffuse through skin cells, but some will travel down hair follicles and reach the dermis layer.

The permeability of skin relative to different shapes of nanoparticles has also been studied. Research has shown that spherical particles have a better ability to penetrate the skin better than oblong (ellipsoidal) particles because spheres are symmetric in all three spacial dimensions. One study compared the two shapes and recorded data that showed spherical particles located deep in the epidermis and dermis whereas ellipsoidal particles were mainly found in the stratum corneum and epidermal layers. Nanorods are used in experiments because of their unique fluorescent properties but have shown mediocre penetration.

Nanoparticles of different materials have shown skin’s permeability limitations. In many experiments, gold nanoparticles 40nm in diameter or smaller are used and have shown to penetrate to the epidermis. Titanium oxide (TiO2), zinc oxide (ZnO), and silver nanoparticles are ineffective in penetrating the skin past the stratum corneum. Cadmium selenide (CdSe) quantum dots have proven to penetrate very effectively when they have certain properties. Because CdSe is toxic to living organisms, the particle must be covered in a surface group. An experiment comparing the permeability of quantum dots coated in polyethylene glycol (PEG), PEG-amine, and carboxylic acid concluded the PEG and PEG-amine surface groups allowed for the greatest penetration of particles. The carboxylic acid coated particles did not penetrate past the stratum corneum.

Increasing permeability
Scientists believed that the skin was an effective barrier to all inorganic particles and alterations to the skin using mechanical stressors causing damage to the skin would be the only way to increase permeability. However, simpler and more effective methods have been developed. For example, ultraviolet radiation (UVR) has been used to slightly damage the surface of skin, causing a time-dependent defect allowing easier penetration of nanoparticles. The UVR’s high energy causes a restructuring of cells, weakening the boundary between the stratum corneum and the epidermal layer. The damage of the skin is typically measured by the transepidermal water loss (TEWL), though it may take 3-5 days for the TEWL to reach its peak value. When the TEWL reaches its highest value, the maximum density of nanoparticles is able to permeate the skin. Studies confirm that UVR damaged skin significantly increases the permeability. The effects of increased permeability after UVR exposure can lead to an increase in the number of particles that permeate the skin. However, the specific permeability of skin after UVR exposure relative to particles of different sizes and materials has not been determined.

Other skin damaging methods used to increase nanoparticle penetration include tape stripping, skin abrasion, and chemical enhancement. Tape stripping is the process in which tape is applied to skin then lifted to remove the top layer of skin. Skin abrasion is done by shaving the top 5-10 micrometers off the surface of the skin. Chemical enhancement is the process in which chemicals such as polyvinylpyrrolidone (PVP), dimethyl sulfoxide (DMSO), and oleic acid are applied to the surface of the skin to increase permeability.

Electroporation is the application of short pulses of electric fields on skin and has proven to increase skin permeability. The pulses are high voltage and on the order of milliseconds when applied. Charged molecules penetrate the skin more frequently than neutral molecules after the skin has been exposed to electric field pulses. Results have shown molecules on the order of 100 micrometers to easily permeate electroporated skin.

Applications
A large area of interest in nanomedicine is the transdermal patch because of the possibility of a painless application of therapeutic agents and very few side effects. Transdermal patches have been limited to administer a small number of drugs, such as nicotine, because of the limitations in permeability of the skin. Development of techniques that increase skin permeability has led to more drugs that can be applied via transdermal patches and more options for patients.

Increasing the permeability of skin allows nanoparticles to penetrate and target cancer cells. Nanoparticles along with multi-modal imaging techniques have been used as a way to diagnose cancer non-invasively. Skin with high permeability allowed quantum dots with an antibody attached to the surface for active targeting to successfully penetrate and identify cancerous tumors in mice. Tumor targeting is beneficial because the particles can be excited using fluorescence microscopy and emit light energy and heat that will destroy cancer cells.