Some New Ideas in Delivery

January 3, 2007

Before an active ingredient can go to work on age spots, wrinkles and other cosmetic maladies, it must reach its target. Here are some of the newest ideas in getting active materials to the skin.

Some New Ideas in Delivery

Before an active ingredient can go to work on age spots, wrinkles and other cosmetic maladies, it must reach its target. Here are some of the newest ideas in getting active materials to the skin.

Tom Branna
Editorial Director

Today’s cosmetics can help hide age spots, diminish the appearance of wrinkles and camouflage blemishes and consumers are willing to pay for all of these disappearing acts. Skin care sales top $12 billion in the U.S. and are growing 5-6% a year, say industry sources.

But before they can work their magic, all of these creams, lotions and gels must deliver their active components to the skin. As the population in the U.S., western Europe and Japan continues to age, cosmetic chemists are putting an increasing emphasis on developing products that adhere to the stratum corneum and penetrate into the upper layers of the skin, to deliver a rich cocktail of peptides, polysaccharides, enzymes, vitamins and botanicals.

To effectively deliver these actives to the skin, cosmetic formulators can choose from a wide array of systems. One of the newest, and most controversial, of course, are nanoparticles. In fact, the personal care industry was one of the first to successfully commercialize nanotechnology with the introduction of nano-sized sunblocks. But like so many other scientific breakthroughs before it, nanotechnology must overcome a host of bad press from nanophobic consumer groups. That said, even seasoned formulators advise some caution when formulating with nanoparticles.

“The nanotechnology that appears to have created controversy in some circles, is seen as a very promising new technology if handled judiciously in carefully formulated products,” observed Shyam Gupta, president of Bioderm Research, Scottsdale, AZ.  “These molecules are so small that some of them can penetrate the cell wall and enter the living dermal tissue and then the bloodstream.”

Dr. Gupta noted that this may not be so desirable for certain materials such as titanium dioxide or zinc oxide for their benefits in sunblock products, as their UV-blocking action is best delivered if they remain on top of the skin and are not absorbed into the deeper layers. The excessive penetration of titanium into bloodstream may, for example, cause safety concerns. Nano-dispersed organic sunscreen agents, such as benzophenones or cinnamate esters, may also pose similar concerns, according to Dr. Gupta.

Yet, when used correctly, nanotechnology can greatly enhance active ingredient delivery. For example, nano-delivered salicylic acid or benzoyl peroxide for anti-acne activity may provide potentially incremental benefits in terms of their increased rate of efficacy, albeit to a possibly shortened duration.

“As one can see, the crossover from  pharmaceutical research becomes of critical importance in determining the specific applications of nanotechnology for topical products,” observed Dr. Gupta.

Bioderm Research has developed an innovative nano-diffusion technology using zeolite molecules for the controlled delivery of certain topical ingredients for a wide range of products including anti-aging and acne treatments. The active molecules are loaded into a zeolite cavity. Upon their application, these molecules are released topically as the moisture from perspiration enters the zeolite cavity, which forces those molecules out due to greater affinity of zeolite for water molecules.

Lessons from Pharma

Dr. Gupta told Happi that cosmetics research is becoming more dependent than ever on pharmaceutical delivery systems. He noted that as marketers desire higher performance products with efficacies approaching those of pharmaceuticals via topical delivery it is inevitable that the ingredients with pharmaceuticals-level efficacy but cosmetics-level regulatory viewpoint will be highly desirable.

“This is not an easy area, as any hint of a drug-type claim in a cosmetic product could trigger FDA interest,” he observed. “New delivery systems specifically designed for a targeted function and utilizing specific ingredients can be of help.”
Salicylic acid, for example, is a very popular anti-acne ingredient approved by the FDA in the U.S. However, it must be formulated at lower pH ranges to provide its optimal anti-acne efficacy. But lower pH ranges are known to cause significant skin irritation. Any neutralization of salicylic acid by common alkali metal or amine bases to a more skin compatible pH is also known to cause a significant loss of its activity. An optimized delivery of sal acid would greatly improve its irritation profile.

Bioderm Research has recently developed zinc amino acid salicylate complexes (INCI: zinc glycine salicylate), which provide both enhanced anti-acne efficacy and more skin compatible pH range with the added benefit of ease in formulating stable products. In the same anti-acne area, Bioderm Research has developed a new “nuclear submarine” delivery system, according to Dr. Gupta.
“It is well known that bacteria such as Propionibacterium acnes require a higher level of iron for their metabolic needs as they multiply at a faster rate than normal human cells,” he observed.

However, this iron must be in [Fe3+] state. The [Fe3+], as in Fe(OH)3, is very insoluble in water. Bacteria utilize molecules called “Siderophores” to collect [Fe3+] and transport it into their cells.

A new natural ingredient that spontaneously binds with the iron part of siderophore forming a radical-anion has been discovered by Bioderm Research. When bound in this manner, siderophore enters Propionibacterium acnes cell and also carries the new radical-anion that is attached to it. This radical-anion then attaches itself to the protein of bacterium.

“This binding simply stops the bacterial multiplication process. It is thus not a true antimicrobial agent, but a ‘nuclear submarine’ that quietly enters the bacterial cell wall and deactivates bacterial metabolic functions that prevent its cellular division,” said Dr. Gupta. “This new molecule is very resistant to oxidation, even by benzoyl peroxide. In combination with salicylic acid or benzoyl peroxide new formulations with enhanced anti-acne  efficacy will be available in the not-too-distant future.”

For years, liposomal phospholipids were the delivery system of choice for many cosmetic formulators. Unfortunately, these materials can chemically degrade by oxidation and hydrolysis, resulting in fusion, aggregation, leakage of their internal contents and other instability problems. As a result, conventional liposomes are mostly impractical for delivery of protein, peptides and enzymes.  

In contrast, microencapsulated liposomes are stable and versatile drug carrier systems that do not have the drawbacks of conventional liposomes, according to Vispi Kanga, president of Cosmet-Pharm Consultants, LLC, Cresskill, NJ.

These liposomes are composed of a wide range of phospholipids in conjunction with polymers such as alginate, chitosan and gelatins. These liposomal microcapsules can also be stored in the dry state as a free-flowing powder.

“This newly developed pharmaceutical drug delivery technology is likely to be fully exploited in topical delivery of anti-aging active ingredients,” predicted Mr. Kanga.

Sun care is often one of the first categories to take advantage of novel delivery systems.
osmetic companies are also borrowing novel patch technology from the pharmaceutical industry. Several marketers, including Estée Lauder and Amore Pacific, have rolled out skin care patches that are based on transdermal iontopheresis, observed Navin Geria, VP-R&D, Spa-Dermaceuticals. In the past, pharmaceutical companies have used this technology to control drug administration through the skin.  Micro-electronic power cells deliver a mild direct current to the upper layers of the skin, resulting in super-hydration and a temporary reduction in the appearance of the wrinkles.

Powders have been used in pharmaceutical products to deliver many materials to the skin. However, the walnut shell powder currently used for many products has uneven edges that can irritate as it exfoliates skin. But now, researchers at Kanebo have a specially-treated powder that provides gentle abrasion without irritation. This technology can be found in Kanebo Silk Peeling Powder.

Raising the Bar on Delivery

Not every novel delivery system is dispensed from a jar or bottle. Twincraft Soap, Winooski, VT has developed delivery systems specifically designed for bar soaps. The technology enables formulators to add actives such as retinol and salicylic acid directly into a soap bar.

“Traditional bar soap manufacturing requires high temperature and pressure, both of which destroy liposome-based delivery systems,” explained Joe Candido, VP-sales, Twincraft. “We’ve developed special soap bases in a temperature-resistant powder, reduced the temperature in our manufacturing environment and modified our extruders so they don’t damage the delivery system.”

The technology enables salicylic acid and retinol to get into the matrix to exfoliate and repair skin, reduce wrinkles and break up comedones. Now, Twincraft has created botanicals that can be added into anti-aging or anti-acne soaps to act as anti-inflammatories. To boost moisturizing properties, the company is testing a compound blend of humectants.

Also in development are self-tanning solutions and a UV protection product that adheres to skin and time-releases active ingredients such as octyl methoxy cinnamate.

“OMC breaks down with time,” explained Mr. Candido. “Our system adheres to skin and releases the active over time.”

As Twincraft prepares to enter the wash-on UV protection segment, it faces stiff competition from Aquea Scientific. The Ventura, CA-based company already markets Wash-On, a patented technology to encapsulate active ingredients into micron sized particles, which are then positively charged. As a result, encapsulated active ingredients are attracted to negatively charged skin and hair.  Active ingredients delivered through the system will remain attracted to the skin and hair throughout the day, even after patting dry. 

An Array of Applications

The technology can already be found in products such as 24-7 Ice Shield Facial Cleanser, which is utilizing the delivery system to incorporate sunscreen with a SPF of 15. In addition to sun protection, the Wash-On system can potentially deliver any active ingredient, including anti-aging, anti-acne, moisturization and OTC pharmaceuticals, among others. Company executives insist they’ve created a third category in personal care.

“Before there was only wash-off and leave-on. Aquea has discovered the wash-on category to deliver active ingredients and make them stick to the skin even in the presence of surfactants,” explained Dave Compton, president of Aquea Scientific. “This isn’t super glue, we believe it’s the best way right now of attracting actives to skin the presence of surfactants.”

The process wraps active materials in a silica wrap that forms a shell and takes on the character of the active material, according to Martin Flacks, head of R&D. The material is then placed in a polymer matrix which imparts a strong cationic charge to the outside of the shell and make it positively charged. Thus, any active will be attracted to negatively-charged skin. The delivery system ensures that the actives don’t penetrate too deeply into skin.

“In traditional formulas, OMC can penetrate 50 microns into the stratum corneum,” explained Mr. Flacks. “But when a product is wrapped in our technology there is a lot of diffusion, penetration is just 10-13 microns.

“So if you put an active ingredient like sunscreen in our system, it stays on the surface and increases the safety of the product.”

Although Aquea Scientific’s initial emphasis is on sun care, company executives insist the Wash On technology has applications in a broad range of anti-aging, skin lightening, even insect repelling products.
From bar soaps to skin patches to nanospheres, marketers realize that when it comes to formulating effective skin care products, more often than not, it’s all in the delivery!