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Intelligent Delivery Systems for Enhancing the Performance of Active Ingredients in Skin Care Formulations

By: Meyer Rosen and Ameann DeJohn
Tel: (516) 922-2167
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The skin is a miraculous organ and the cosmetic & personal care industry continues to make improvements on how to maintain the health and beauty of this organ, the largest in the body. Much of the radiant youthful glow on the skin is often achieved through the delivery of advanced, active skin care products. These products are designed to work effectively on the surface of the skin. However the performance of the most effective products are boosted by new active ingredient technology and most importantly by new targeted systems that deliver the active ingredients to defi ned areas of the skin in order to achieve the most desirable results.

Delivery system technology can be divided into two areas. The first is "surface/topical" delivery- as defined by the FDA in the U.S. as "cosmetics" and the second is delivery below (into/past) the "surface". Depending upon the depth of penetration and whether the material gets into the blood stream, such materials are characterized by the FDA as "drugs", or in industry parlance -API's (active pharmaceutical ingredients). There is a gray area between the two legal distinctions and this is unregulated. Into this breach, the industry has spent much research and time to develop active ingredients that have been shown and claimed to provide performance craved by the rapidly increasing consumer demand from both seniors and their progeny.

As the quest for youthful skin continues, the market for anti- aging skin care is exponentially accelerating. Thousands of formulas exist that promise the key to youthful, vibrant skin. However, for the active ingredients in these skin care formulations to perform optimally, they must penetrate into the targeted areas of skin and perform specifi ed claimed advantages. Actives that "sit" on top of the stratum corneum, the dead cellular level, will provide only temporary and minimal benefits. Actives that are delivered deeper into the living layers of skin cells are able to work more effi ciently and make signifi cant changes in skin appearance and quality. The key to achieving this improvement is how and when the actives are delivered, and what trigger is employed to deliver them to the most beneficial destination on/in the skin.

Actives penetration into the layers of skin can be achieved by means of carefully designed delivery systems. These systems serve as a "vehicle" for the delivery of active ingredients into the skin layers. Such targeted delivery systems have been instrumental in optimizing the effectiveness of expensive, often degradable active ingredients. If the actives degrade, do not penetrate, or are not delivered to the proper sites, they will not be employed to their full extent, and may not live up to their full potential of benefits and claims.

Skin Penetration Mechanisms

The skin can be penetrated via two general mechanisms: physical means or chemical means. Types of physical penetration mechanisms include iontophoresis, or use of a small electric charge, electrical currents, thermal, light or ultrasound energy. Chemical penetration can be achieved by means of: organic solvents, fatty acids, alcohols, surfactants, or proprietary enhancers. While facilitation of chemical penetration techniques can be characterized as "simple" delivery systems, there are other more complex approaches to achieving the described goals. Current formulas use a variety of these ingredients in many different combinations and spatial arrangements to act as more sophisticated delivery systems.

Whether entering the skin physically or chemically there are three types of methods to achieve cell layer penetration. Transcellular Penetration goes into and through the stratum corneum cells. Intercellular Penetration goes around and through the overlapping stratum corneum cells. Transappendageal penetration takes other pathways in the skin, such as through the openings around hair follicles via sebaceous glands and into sweat glands. The transappendageal route is known as a shunt route and is less important as it represents a small penetration area of the total skin surface.

Delivery systems produce beneficial enhancement of active ingredients and they help the skin obtain the maximum benefits attainable. Due to expanding and more restrictive global regulations on skin care ingredients, one "low hanging fruit" approach to success is to utilize skin-value ingredients already on the market but make them more effective. Essentially, we want our existing, accepted, active ingredients to perform and safely produce well documented beneficial results to work better than when used alone. To accomplish this a successful delivery system is the key to creating formulas that deliver the ingredients and obtaining the desired results.

Let's take a look at some of the various types of delivery systems available to the skin care market

  • Liposomes are known as the first generation of novel delivery systems. These have been the choice delivery approaches of many skin care and cosmetic formulators for many years. Liposomes are hollow, fluid-like vessels (vesicles) in spherical shape, which contain one or many lipid layers. These fluid-like spheres bring the active ingredients into the skin and are then slowly released.
  • Niosomes are vesicular systems similar to liposomes and can be used as carriers of amphiphilic and lipophilic drugs or cosmetic actives. A major cosmetic company fi rst devised them for cosmetic applications. Niosomes are non-ionic. They are generally less toxic than the ionic types, and improve the therapeutic index of cosmetic actives or API's by restricting their action to target specific cells.
  • Microcapsules are a well-known and long existing commercial offer the same benefit as liposomes and provide time-release of the active ingredients. These are generally of small spherical or oblong shape with an internal core or "fill" and an external shell or membrane. Microcapsules require a shearing stress in the form of rubbing to disrupt the shell and release the internally held active ingredients. This characteristic is ideal for topical cosmetics and personal care products. However, it is essential to design the strength of the microcapsule wall so that the shear rate induced by the topical application (i.e. rubbing) will disrupt the membrane wall and release the contained active ingredients. In recent years, the microencapsulation approach has morphed towards systems with improved stability and effi cacy in delivering actives. Multi-layer spheres are now capable of stabilizing both hydrophobic and hydrophilic actives- thereby preventing oxidization and discoloration of the finished formula.
  • Nanotechnology is relatively new to the cosmetics and skin care world, however the original technology has been in existence since 1959. Nanotechnology refers to a delivery methodology into and through some or all of the skin layers by means of a nanometer sized particles, approximately one-billionth of a meter. Such particles can only been viewed through very powerful microscopes. There is much controversy surrounding this technology in terms of potential safety, or lack thereof, in view of the fact that for cosmetic use it is speculated, or demonstrated in some cases, that contained actives may reach the bloodstream in view of their ability to cross cell membranes. The FDA (U.S.) and Royal Society (UK) have issued statements calling for continued, appropriate testing. This is an emerging field with many variations and the anticipated path of safety evaluation, for each individual nanoparticle type is a long road yet to be travelled.
  • Microsponge Technology is a patented, polymeric delivery system that is non-irritating, non-mutagenic, non-allergenic, non-toxic and non-biodegradable. The appeal of microsponges stem from their ability to overcome the difficulties experienced with conventional delivery systems, and their capability to effectively release active ingredients over an extended period of time.
  • Hydrogels are sustained release delivery systems which are hydophillic polymers. Plants, seaweed, animal tissue and chitin are all examples of hydrogels found in nature. Hydrogels swell with imbibition of the external aqueous phase and such swelling is dependent upon the polymer(s) employed as well as other factors. It is widely believed that hydrogels offer a viable pathway of absorption/ release of hydrophilic ingredients.
  • Aspasomes were originally formed when ascorbyl palmitate was explored as a bi-layered vesicle. Aspasomes can encapsulate hydrophilic ingredients and enhance skin permeation.
  • Organogels are clear, thermodynamically stable, viscoelastic and biocompatible jelly-like phases composed of hydrated phospholipids and an organic liquid.
  • Patch Delivery Systems are release liners that deliver the active through the skin. Patch Delivery Systems were developed for the pharmaceutical companies to control drug administration through the skin. However, cosmetic companies are now borrowing the patch technology for cosmetic use and this pathway serves as an excellent example of actives transfer as well as technology transfer!
  • Patch systems deliver actives through five components. The liner protects the patch while not in use. The active pharmaceutical ingredient, or cosmetic active, is impregnated into the patch. The adhesive binds the components of the patch and adheres to the skin. The membrane controls the release time for the active. Lastly, the backing is the part exposed to the air, which protects the actives at all times. These parts work as the sum of the whole to infuse the active into the skin.

  • Proprietary delivery systems designed for specific products
  • Niadyne, Inc. uses a patented MicroNutrient delivery system in their 24 skin care products. Micronutrient delivery allows ingredients to penetrate the epidermis in slow, continuous release. This allows time for the molecule to bio-convert to its working form.

    Conrex PET (Permeation Enhancement Technology) is one of the few proprietary enhancers that have FDA approval in the U.S., and has been clinically shown to deliver molecules transdermally. The method works topically as well and this capability has been demonstrated to increase actives' efficacy. In view of the fact that PET is composed of naturally occurring compounds that are non-toxic, non-irritating and non-allergenic, it is considered a "safe" penetration enhancer.

    PET™ works by solubilizing the active ingredient(s) within the polymeric matrices and temporarily modifying the permeability of the skin. This approach enables large, selected molecules to pass between and through the skin cells of the stratum corneum, stratum lucidum, stratum granulosum and ultimately reaching the deeper layers of the skin (stratum spinosum, stratum basale). This delivery system can be found in SESHA Cosmeceutical skincare products.

    Transferosomes are supramolecular delivery system bodies that can pass through a permeability barrier. They are more elastic than liposomes. Transfersomes technology is drawn to water and these ultra-deformable vesicles can be loaded with active ingredients. When the technology is used in cosmetic formulas the carrier searches and exploits the hydrophilic pathways. This process permits the vesicle to pass through the barrier and release the active. This is the proprietary technology of a drug delivery system developed by a German company known as IDEA AG.

  • Lipoderm® Core, is a proprietary and patent-pending blend of ingredients that claims transdermal action when added to an emulsion. Lipoderm® Core improves effi cacy and delivery of active ingredients in personal care formulations. The technology works by creating a small amount of disorganization in the stratum corneum, thus opening up channels in the lipid matrix of the skin. The technology is effectively with a large number of chemical structures, both polar and non-polar and is available from PCCA.
  • Transcutol™ CG (diethylene glycol monoethyl) has the ability to attract and hold water. It is soluble in both water and oil and capable of forming an intracutaneous API depot, or reservoir, for the active ingredient. Transcutol™ CG is easily combined with polar and non polar solvents. It is highly valued because of its bio-compatability with the skin and has great solubilizing properties. Transcutol™ CG is the available from Gattefosse.

    ActivBoost by Technology Recovery Systems, LLC is a unique, patented anti-aging, moisturizing delivery system that is nonirritating and all natural. In a time predictable and reversible manner, ActivBoost's Hydroxide Releasing Agent (tm) system is capable of delivering many actives to and into the skin in dosages previously thought to be impossible. The ActivBoost system works by creating water channels in the stratum corneum. These channels provide a method of delivering both hydrophilic and lipophilic molecules to the skin and surrounding tissues. All the components of ActivBoost are on the FDA's IIG list.

  • Retinol Molecular Film Fluid is a new cosmetic delivery system specifically created for retinol (the well known effective anti-aging active) that ensures stabilization of the oxidatively sensitive molecule and enchances cutaneous absorption of Vitamin A through the epidermis.
  • Invisicare Polymer delivery system is specifically formulated to carry water insoluble actives and certain cationic active ingredients in water-based products without the use of alcohol, silicones, waxes or other organic solvents. Invisicare Polymer is a patented polymer delivery system with a unique formula and process for combining active ingredients in a delivery system that extends the duration of time the active remains on the skin and active.

Foreseeable Challenges and Future Value of Delivery-Systems-to-Come

Challenges proliferate when working with skin care delivery systems. There is not a one-size-fits-all system. Advanced active ingredients must be correctly paired with delivery systems that work to deliver their benefits most effi ciently and yet remain stable and intact. However, it is important in such systems that the actives do not become too potent since this can lead to potential toxicity.

Whichever method of delivery is chosen, delivery systems provide a better functioning product. Moreover, they provide numerous attractive aspects for the consumer. In general, consumers may initially purchase products because of claims and social media input. However, delivery systems may assist in the claims that can be made for products because of the value they add. When companies develop their delivery systems, they typically conduct trials that demonstrate the product's efficacy. This information easily transforms and can be effectively translated to interesting marketing claims for your product. By using a delivery technology one is able to develop products with immediately perceivable and long-term results. Later, customers repeat purchase because of performance they can see and feel. These claims differentiate products from the competition and provide credibility.


Using a delivery system creates a superior product that penetrates more effectively and feels better on the skin. All of these attributes are infl uential on consumer behavior and repeat spending patterns. Products with delivery systems to boost the actives penetrate more deeply thereby providing enhanced efficacy and generate enhanced product performance and future sales.

From a value point of view, the U.S. market The market has increased from $19 billion in 2000 to over $41 billion in 2007, according to the Journal of Cosmetic Science. With a doubling in sales in only seven years, we can expect even more growth in the next decade. Further, the market is likely to continue to grow as companies continue to improve upon delivery technologies and consumer demand drives the need for better and more effective skin care products. When it comes to formulating effective skin care products, more often than not, it's all in the delivery!

Meyer R. Rosen, President of Interactive Consulting, Inc., is a Nationally Certified consulting chemist/chemical engineer and an experienced forensic expert witness for plaintiff/defense attorneys and insurance companies in both Federal and State cases. I provide technical guidance in personal injury, product liability, intellectual property and trade secret matters. My background includes over 35 years of in­dustrial and fifteen years of academic experience. Areas of expertise include, but are not limited to: fires, explosions, hazardous chemicals, chemical fires, chemical exposure, toxic exposure, chemical burns and cosmetic science. Common cases are typically associated with: household & industrial products, specialty chemicals, cosmetics and hair relaxers. I am also experienced in analysis of industrial accidents, technical aspects of warnings, instruction & labels, OSHA reg­ulations, and Codes & Standards.

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