Your Nails and You

Monday, March 11, 2024

Evolutionary Purposes of Nails

Over time, humans’ fingernails and toenails have evolved from claws to what they are now. It is believed that human ancestors utilized claws to grab onto things, dig holes, and climb tree trunks. However, as they grew larger, these claws got in the way as they climbed up trees and attempted to grab small branches in search of food. Claws also hindered our ancestors’ ability to grab small items or pick up bugs. Another evolutionary benefit of nails is that they are thought to have supported the development of broad fingertips, enabling our ancestors to develop grip.¹

Toenails also started as claws and went through a nearly identical evolutionary development to fingernails. Like the claws on the hands, clawed feet were useful to get a grip when climbing up trees. However, they got in the way of movement on the ground.

The development of fingernails and toenails also serves as protection; the hard surface of nails protects the tissues, nerves, blood vessels, and muscles beneath them.²

Nail Physiology

Nails are composed of several strands of keratin that are bound together by disulfide bonds. The low lipid content of the nail layer, combined with its molecular composition of keratin molecules communicating across disulfide linkages, makes its behavior similar to that of a hydrogel and separates it from other body barriers. The nail plate grows from the nail matrix, arises from the crease of the proximal nail fold, and is kept in place by the lateral nail folds (Figure 1). The nail plate also protects the nail bed (sterile matrix and germinal matrix). Intercellular attachments, desmosomes, and membrane-coating granules keep the cells of the nail plate intact.

Figure 1. Cross section of a nail and basic anatomical features

In addition to the nail plate, other important components of the nail are the nail matrix, nail bed, cuticle, and nail folds. The nail matrix is found under the skin at the proximal tip of the nail. It is the area where new fingernails and toenails start to grow. The nail bed is made of the sterile matrix and the germinal matrix. This area of the nail is a thin epithelium where the nail plate adheres and slides as it develops. The sterile matrix lies underneath the nail plate and attaches it to the distal phalanx. The germinal matrix is the area of soft tissue proximal to the sterile matrix. The cells in this area of the nail divide and become keratinized, forming the nail plate.³

The cuticle is simply the layer of skin located at the nail bed, near the base of the nail (Figure 1). Nail folds are areas of skin that enclose the nail plate at its lateral and proximal ends. Lateral nail folds are the cushioned lateral margins of the nail, and they participate in the nail’s adherence to the nail bed. The proximal nail folds are on the nail’s dorsal side and conceal the whole nail matrix or just a portion. These folds work with the cuticle to protect against irritants, solvents, and other agents that would disrupt matrix function and nail formation.⁴

Problems and Diseases

Figure 2. Image showing the three stages of nail infection

Sometimes, issues occur with the nail due to environmental or internal factors such as malnutrition, irritation, care issues, or genetic disorders. Psoriasis is a skin condition with raised red patches of rash caused by many factors, e.g., irritation, genetic conditions, and infections, and can affect various parts of the body including nails. Nail psoriasis on the nail matrix causes pits or ridges to form in the new nail, while damage to the nail bed can cause it to turn yellow or red and become thickened which can then lead to nail cracking or falling off.⁵ In general, nail infections can be divided into three stages (Figure 2).

Nail-patella syndrome is another genetic disorder that is much rarer and causes the absence or shrinking of the nails and kneecaps along with some other bone deformities.⁶ The most common symptom is missing or underdeveloped nails. Koilonychias, i.e. spoon nails, is a condition caused by trauma such as nail biting where the nail plate curves upwards instead of down. Paronychia is inflammation of the nail folds caused by pollution or alkali chemicals in chronic cases or bacteria (e.g., staphylococcal) in acute cases.⁷

Many different organisms can infect the nail or surrounding tissue and cause cosmetic issues, pain, or damage. Pseudomonas bacteria can infect nails either between the nail bed and nail plate or between an artificial nail layer and the nail plate normally due to having water underneath nails and poor hygiene. This causes green discoloration, nail plate weakening, and sometimes nail plate separation in the case of bed-plate infections.

Onychomycosis nail fungus is responsible for the majority of issues with nails and thus, it is the most widely studied, affecting anywhere from 10-40% of the population. Some genetic or health factors can predispose someone to get the infection and poor hygiene can increase risk, but nail fungus can infect almost anyone. Nail ringworm, contrary to its name, is not caused by a parasitic worm and is instead a type of onychomycosis sometimes falsely referred to as tinea unguium, which is just another name for nail fungus, in general. This infection is marked by rings of inflammation, distortion, thickening of the nail, and ultimately resulting in nail plate amputation.

Drug Treatments

There are many different treatments for nail infections. Nail oils are a common herbal remedy that is used for nail diseases. Some nail oils contain active ingredients, while others do not. Two nail oils that contain active ingredients are Better Nail and Fuginix. Better Nail contains 25% Undecylenic Acid, as well as other essential oils such as Tea Tree Oil, Lavender Oil, and Jojoba Oil. Fuginix also contains Undecylenic Acid, but less than in Better Nail. Its other ingredients include oils such as Tea Tree Oil, Lavender Oil, and Jasmine Oil. On the other hand, many nail oils do not contain any active ingredients (Kerassentials Nail Oil and H-Nail Fungus Formula). These both contain essential oils, as well as other herbal ingredients, to treat nail infections. It has been shown that nail oils that contain an active ingredient are more effective at treating nail infections.⁸

Other products, such as creams and oral medicines, are also used to treat nail infections. Many different drugs can be used in any of these products. Some drugs that may be used in antifungal creams are Efinaconazole (Jublia^®), Tavaborole (Kerydin™), and Urea (in Umecta). Drugs that are often taken orally to treat nail infections are Terfenadine and Itraconazole. Terfenadine works best for skin infections around the nail but can have severe side effects, while itraconazole works best on yeast and mold on the nail. Based on the data from the National Institute of Health, 144 clinical trials are currently undergoing to study nail fungal infections. Following are the percentages of clinical trials for a few key drugs - 7.6% tavaborole, 4.9% itraconazole, 4.2% urea, and 3.5% efinaconazole. Other microbial agents used to treat nail infections are amoxicillin, clindamycin, sulfamethoxazole, trimethoprim, bacitracin, gentamycin, mupirocin, fluconazole, nystatin, ciclopirox, amorolfine, terbinafine, griseofulvin, and polymyxin B sulfate.

Dosage Forms and Delivery

Oral drugs are a prevalent form of drug delivery for nail infections. Specifically for fungal infections, oral treatments are used when more than half of a nail is covered, or if more than three nails are affected. While they can be very effective, oral therapies have numerous limitations. These limitations include a lack of patient compliance, a high risk of recurrence, significant adverse effects, and contraindications. Oral treatments are often used for fungal infections in nails but these tend to cause systemic side effects, such as liver toxicity.

Topical drug delivery, and specifically transungual drug delivery, is another type of drug delivery that is commonly used for treating nail infections. One type of transungual nail delivery form is nanoemulsion. Nanoemulsions are droplets of liquid and surfactant mixtures that are 10-500 nm in size. They are often distributed in the form of a gel (“nanoemulgel”) and possess all of the properties needed for antifungal therapy. These properties are stability, improved solubilization, increased permeation effect, and targeted action. Nail patches can also be used for treatment, and are effective due to their non-invasive characteristics, serving as a means to eliminate adverse effects of oral and injected therapies.⁹

Nail lacquers are made by suspending a drug in a solvent with a polymer so that when added to the nail, the solvent evaporates and leaves behind a polymer film containing the drug. This allows the drug to be released over time, allowing for more penetration of the nail plate and avoiding having to reapply as often.¹⁰ Methods have also been developed through biomimicry to create artificial lysosomes, which are bi-layered phospholipid vesicles filled with a drug solution. This makes them good for drug delivery in hydrophilic and hydrophobic environments and allows them to store ethanol for non-water-soluble drugs.¹¹

Some experimental methods are being developed to supplement topical treatment due to the lower efficacy rate compared to the oral routes. Iontophoresis is the process of adding a topical medication to the nail and then applying a localized electrical current to the area to allow the particles to pass through. Ultrasonic nail drug delivery is similar except it uses short bursts of short-wavelength, high-intensity sound to source particles through the nail. The nail can also be etched either using very small scratching to the surface or chemicals such as weak acids to remove some of the top layers of keratin and allow the drug to travel deeper in the nail.¹²

In spite of advanced medicines and drug delivery systems, it takes months to treat nail infections, and more work is needed in this area.

References

Knott, L. (2019). Why do we have nails? https://patient.info/news-and-features/why-do[1]humans-have-nails#:~:text=It’s%20 thought%20that%20 nails%20are,branches%20 in%20 search%20 of%20 fruit
Meyer, A. (2019). Curious Kids: why do we have fingernails and toenails? The Conversation. https://theconversation.com/curious-kids-why-do-we-have-fingernails-and-toenails[1]110989#:~:text=The%20short%20 answer%20 is%20 we,fingernails%20gene%20 to%20their%20kids
TeachMeAnatomy. (2021). The nail unit - plate - germinal matrix - bed - TeachMeAnatomy. https://teachmeanatomy.info/upper-limb/misc/nail-unit/
Bhattacharjee B, Dey N, Barman D, Karmakar A, Ahmed N, Understanding the drug delivery through nails: a comprehensive review, Journal of Drug Delivery and Therapeutics. (2021); 11(4):116-131 DOI: http://dx.doi.org/10.22270/jddt.v11i4.4941
Nenoff, P., Paasch, U., & Handrïck, W. (2014). Infektionen an Finger- und Zehennägeln durch Pilze und Bakterien. Hautarzt, 65(4), 337–348. https://doi.org/10.1007/s00105- 013-2704-0
Nail-patella syndrome - About the Disease - Genetic and Rare Diseases Information Center. (n.d.). https://rarediseases.info.nih.gov/diseases/7160/nail-patella-syndrome
Professional, C. C. M. (2023). Nail infection (Paronychia). Cleveland Clinic. https:// my.clevelandclinic.org/health/diseases/15327-nail-infection-paronychia
Top 5 Fungus Under and Around the Nail Remedies of 2023: Which Brands Think You’re Stupid? (2023). Top Fungus Alert.
Transungual (NAil) drug delivery – Michniak Laboratory for Drug Delivery. (2023).
Shanbhag, P. P., & Jani, U. (2017). Drug delivery through nails: Present and future. Eur. J. of Molecular and Clin. Med., 3 (5), 252. https://doi.org/10.1016/j.nhtm.2017.01.002
Tanrıverdi, S. T., & Özer, Ö. (2013). Novel topical formulations of Terbinafine-HCl for treatment of onychomycosis. Eur. J. of Pharm. Sci., 48(4–5), 628–636. https://doi. org/10.1016/j.ejps.2012.12.014
Dr, S. N. (2013). NAIL DRUG DELIVERY SYSTEM. ResearchGate. https://www.researchgate. net/publication/255758355_NAIL_DRUG_DELIVERY_SYSTEM

Editor’s Note: Hemant Joshi and his colleagues at Tara Innovations are frequent contributors to American Pharmaceutical Review and Pharmaceutical Outsourcing magazines. Tara offers summer internships to students interested in science. During their internship students learn how science is applied to real-world situations. American Pharmaceutical Review supports their efforts by publishing articles written by their interns.

Author Details

Sienna Dragone, Natalie Devine, Neelam Sharma and Hemant Joshi - Tara Innovations LLC; www.tarainnovations.com;[email protected]

Sienna Dragone is a high school senior at the Morris County School of Technology, in Denville, NJ, in the Academy for Biotechnology. She is planning to pursue a career in chemical engineering.

Natalie Devine is a high school senior at the Morris County Vocational School of Technology studying in the Academy for Biotechnology. She is pursuing a career in biology and genetics.

Publication Details

This article appeared in American Pharmaceutical Review:

Vol. 27, No. 2

March 2024

Pages: 48-50

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