Nanotechnology for dermal drug delivery involves encapsulating drugs in small delivery vehicles (usually 20-300 nm) to allow for easier penetration through the skin barrier and sustained drug release. The most common examples of these vehicle types include liposomes, niosomes, polymeric particles, solid lipid nanoparticles, dendrimers and nanocrystals. At present, the vast majority of these types of delivery systems exist only in either research or early development stages, with the lack of available long term safety data being the single largest limitation.
For the average reader, this is for educational purposes and is not intended to be used as medical advice. Please consult with a doctor (dermatologist) prior to starting any type of skin care regimen.
Why it is difficult to penetrate the skin with drugs
The primary challenge in topical therapy stems from the skin’s effective barrier function. This outermost layer, the stratum corneum, is only 10 to 20 micrometers thick, but blocks almost anything trying to pass through it. You can think of this layer as dead cells stacked up like bricks with lipids filling the space between them as if they were mortar.
One such example would be the 500-Dalton Rule, which is used as a general rule of thumb for estimating if a compound can permeate through the intact skin without any additional help. Normally, molecules that have a molecular weight greater than 500 Da find it difficult to pass through intact skin-this is a big problem because most new medicines are quite large.
Dermal delivery focuses on treating issues with the skin such as acne, psoriasis, and eczema. Transdermal delivery passes through the skin into the bloodstream such as a nicotine patch. Both are being studied using nanocarriers, however there has been much more progress in the area of dermal delivery.
What nano actually means here
The definition of a nanomaterial is a material that has at least one dimension within the approximate range of 1 to 100 nm. This is the definition used by regulatory agencies, and the European Union uses it as part of their cosmetics regulations. However, in the field of skin research there are several types of nanocarriers (carriers) which have larger dimensions such as 100 to 300 nm but are still referred to as nanocarriers.
Why does size matter? The smaller the particles, the greater the surface area for each unit mass. Therefore, these smaller particles will dissolve faster, adhere to the skin more effectively, and may be engineered to slowly deliver a drug.
The main types of nanocarriers
|
Carrier |
What it is |
Best known for |
|
Liposomes |
Spheres made of phospholipid layers |
Carrying both water-loving and fat-loving drugs |
|
Niosomes |
Like liposomes, but built from non-ionic surfactants |
Lower cost, good stability |
|
Transfersomes and ethosomes |
Flexible, softer vesicles (ethosomes contain ethanol) |
Reaching deeper into skin than standard liposomes |
|
Polymeric nanoparticles |
Made from PLA or PLGA |
Slow, controlled release |
|
SLNs and NLCs |
Solid or semi-solid lipid particles |
Stability, skin hydration, sun protection |
|
Dendrimers |
Branched, tree-like molecules |
Carrying small drugs and peptides |
|
Nanocrystals |
Pure drug ground down to nano size |
Improving poorly soluble drugs |
Liposomes and niosomes
Liposomal flexibility enables drugs containing both hydrophilic and lipophilic characteristics to reach the skin. The majority of the liposomes are thought to be relatively safe for skin use. There is a common misconception about the ability of regular liposomes to penetrate through all skin layers up to the dermal layer. Preclinical and in vitro studies have found that some of the flexible liposomes, such as transfersomes and ethosomes, have the potential to penetrate the skin deeper than regular liposomes.
Niosomes function on a principle similar to that of liposomes. As surfactants are more cost effective and have better stability compared to phospholipids, niosomes present an appealing option to companies that manufacture pharmaceuticals.
Polymeric nanoparticles
Polymers (PLA and PLGA) that the human body is able to break down are currently utilized in the manufacture of medical devices (i.e., biodegradable sutures). Skin research finds value in using these polymers as well, since the polymer allows for a gradual release of the active ingredient(s); therefore, reducing the required application frequency.
SLNs and NLCs
Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are both composed of lipids that remain in a solid state at normal body temperatures. NLCs incorporate a liquid lipid into their composition; therefore they have more space available for drugs to be encapsulated within them and also allow less leakage of drugs during storage. Research in this area primarily focuses on treatment of ailments like acne, psoriasis, and fungi-related illnesses.
Dendrimers
Dendrimers are made of multiple branches with each of the branches having the ability to be altered. Therefore, dendrimers are highly versatile instruments. However, it takes a great deal of money to make dendrimers. Additionally, concerns remain regarding potential cytotoxicity associated with certain dendrimer structures. Most of the research carried out on dendrimers is being done in laboratories.
Nanocrystals
No separate carrier is present here. The drug is ground to a nanometer level to assist in dissolution and distribution over the skin surface. This is one of the simpler concepts, and therefore, one of the more feasible.
How nanocarriers help the drug
Better penetration. Small particles may enter your body through the tiny spaces between each of the cells on your skin and through the openings of your hair follicles. Moreover, hair follicles act as an accumulation place for substances. That is why they play such an important role in treating acne cases.
Slow release. Release of the drug slowly from the carrier makes for a sustained effect, unlike rapid absorption of the topical drugs. It provides relatively stable changes in the blood content when contrasted with the fast absorption of topical medication.
Targeting. Some particles can be covered with antibodies or peptides in order to target particular kinds of cells; but this approach is still experimental.
Where it is being used or studied
- Acne and psoriasis: The inclusion of retinoids or corticosteroids will decrease their redness and peeling effects on skin.
- Skin cancer: Studies on carrier systems which will transport chemotherapeutic agents to the basal cell carcinoma and melanoma without damaging other tissues are underway.
- Wound healing: The particles which contain either antimicrobial or growth-promoting agents are undergoing tests for the treatment of chronic wounds, burns, and ulcers caused by diabetes.
- Anti-aging products: Antioxidants and peptides that can be delivered using lipids are popular in skincare; however, there isn’t much evidence of their drastic effectiveness.
- Sunscreens: Zinc oxide and titanium dioxide, which have nanosize particles, have been frequently used in sunscreen products because they do not cause any whitening of the skin. To date, studies show these materials remain primarily on the surface of intact skin.
It must be noted that at the moment, only a small number of nanoskin products have been put on the market. Many studies performed in labs and animals do not guarantee the same results when tested on people.
Safety, rules and manufacturing
Safety. The primary concerns include issues such as skin irritation, allergies, particle accumulation over time. It may be especially true for the cases of damaged or sunburned skin. Long-term human safety data remains limited.
Regulation. More rules are being set but the rules differ based on the area involved. Guidance documents have been released by the US Food and Drug Administration in 2014 on the criteria used to determine whether a particular product is a nano-based product. Under the European regulation EC 1223/2009, cosmetic substances that are considered nanomaterials have to be notified and labeled with [nano].
Manufacturing. Production of uniform size and quality particles batch after batch without being too expensive proves to be quite difficult. This is a primary reason why laboratory success has not yet translated into commercial products.
What to expect next
Nowadays, nanocarriers are combined with technologies like microneedles to enable delivery of large molecules through the skin barrier. The need for personalization of treatment and further investigation of safety aspects should also be noted. There are no breakthroughs, only a consistent approach, and the first products to come are going to be the most simple ones – nanocrystals and lipids among others.
Key takeaways
- The stratum corneum is one of the major reasons why many drugs have problems entering the skin.
- Nanocarriers aid in penetration, providing controlled release and at times cell targeting.
- Different types of nanocarriers perform differently and no carrier is the best for all applications.
- Most of the studies reported are preclinical; therefore, be careful when making claims based on product labeling.
- Safety issues and production are still major challenges.
Frequently asked questions
What is nanotechnology in dermal drug delivery?
This involves the use of very small drug-carriers or particles that aid in the penetration of the drug into the body through the skin for therapeutic purposes.
Is dermal delivery the same as transdermal delivery?
No. Dermal drug delivery uses the skin alone. Transdermal drug delivery, on the other hand, is drug delivery through the skin and into the bloodstream, such as nicotine patches.
Are nanoparticles in skincare safe?
For healthy skin, scientific researches that have been done regarding common ingredients like nano zinc oxide show very low absorption rates. Safety may vary depending on the material, size and condition of the skin.
Which nanocarrier is best for the skin?
There is not one winner. There are liposomes for moisturizing formulas, SLN/NLC for formulas with stability, and nanocrystals for poorly water-soluble drugs.
Can nanoparticles reach the bloodstream through skin?
However, they remain mostly intact skin. Certain smaller or more flexible molecules are able to get deeper into the skin, in case it is compromised or very permeable.
Are there nano-based skin treatments available now?
Yes, primarily in cosmetics sunscreens. Prescription formulations are relatively rare and have many potential candidates in the works.
Sources and further reading
- Bos JD, Meinardi MMHM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Experimental Dermatology, 2000.
- Prausnitz MR, Langer R. Transdermal drug delivery. Nature Biotechnology, 2008.
- FDA of US. Consideration of whether a product regulated by FDA involves the application of nanotechnology (guidance, 2014).
- Regulation (EC) No 1223/2009 on cosmetic products (EU). Provisions concerning nanomaterials.
- Reflection papers on medicinal products containing nanotechnologies (European Medicines Agency).