Delivery Systems

TRANSDERMAL DELIVERY SYSTEMS

Because one of the functions of the skin is as a barrier to protect the internal environment of the body, this barrier function must be overcome to enable the external penetration of beneficial cosmeceuticals. Transdermal delivery systems have been developed to modify this barrier function of skin and can be categorized in two mechanism groups, chemical and physical.  Electric current, thermal, light, and ultrasound energy are all examples of physical penetration enhancement systems that have been used in the medical and esthetic fields successfully for decades. However, cost is prohibitive for home care use.  Also, concerns regarding the uniformity of current, distribution of energy, destruction of the skin, and the ability to control ionic properties require trained practitioners.

The impracticality of physical enhancers makes chemical based delivery systems far more attractive and viable for the pharmaceutical, cosmeceutical and skincare purposes. Commonly referred to as “penetration enhancers”, chemical delivery systems used for cosmeceutical uses should be safe, non-toxic, pharmacologically inert, non-irritating, and non-allergenic. Additionally, once the active ingredients are allowed to penetrate through the stratum corneum (SC), the penetration agent should disperse and allow the skin to quickly revert back to its normal barrier properties.  Some chemical enhancers such as alcohol are effective as penetration enhancers but will ultimately dissolve skin lipids, irritate and dry out the skin thus counteracting the benefits of the active ingredients.  Such safety and tolerability issues greatly reduce the compatibility of many chemical enhancers for long-term topical use.

A common chemical enhancement technology is liposomes – microscopic vesicles or hollow spheres containing one or several lipid bi-layers that surround a hydrophilic watery nucleus.  However, liposomes are highly fragile, and lack substantial proof showing that they enable active agents to significantly penetrate past the epidermal stratum corneum intact.  Thus, much of the benefit from liposomal formulations is a transient effect only on the surface layers of the epidermis. This limits the dependability of liposomes for cosmeceutical delivery purposes.  Recently, variations of liposomes have also been applied to skincare.  For example, encapsulations – micron-sized capsules that hold cosmetic actives in a matrix of membrane-like vessels, microsponges – an entrapment technology with a network of void spaces that are used to hold the entrapped ingredient, multiple emulsions, microemulsions, microspheres, mineral spheres, and skin patch technologies have all been used to transfer ingredients to the sub-epidermal level.  All these micro encapsulating methods employ a variety of rate controlling mechanisms to gradually release active ingredients to the skin in an attempt to provide longer exposure time and deeper penetration into the deep layers of the epidermis and dermis.

Even nano-science, which involves development of solid particles and capsules in the submicron diameter (nanometer) range, is playing a role in skincare. However, consumer reaction against nano-technology is on the rise because of evidence that some nano-particles may uncontrollably penetrate through the dermis into the systemic blood flow.  The lack of control of such penetration allows some nano-particles used in pharmaceuticals to enter the bloodstream or cross the blood-brain barrier of the central nervous system.  Further refinement of this technique is ongoing for the success of nano-technology in the pharmaceutical industry.

A more suitable method of chemical penetration enabled delivery is the use of biodegradable polymeric matrices that deliver cosmetic molecules through the SC for deeper penetration.  In this type of technology, a combination of cosmetic actives are formulated within polymeric matrices containing natural penetration enablers and then released into the skin via hydrolysis or enzymatic degradation. These polymeric cosmetic conjugates can be designed to target specific treatment areas providing substantially improved results. This approach is particularly suited to the delivery of large molecular weight substances such as peptides, amino acids, lipids, vitamins, hormones and other bio-actives.

SESHA SKIN THERAPY’s PET™ delivery technology employs this type of polymetric matrix in its approach to cosmeceutical skincare.  PET™ works by solubilizing the active ingredient within the polymeric matrices and temporarily modifying the permeability of the skin, thus enabling large molecules to pass between and through the skin cells of the stratum corneum, stratum lucidum, stratum granulosum and reaching the deeper layers of the skin (stratum spinosum, stratum basale) (see figure 1).  The major drug route of drug transport across the stratum coreum is the intercellular pathway.  Figure 1 clearly shows the intercellular space between the dead stratum coreum.  It is composed by lipid materials (ceramide, cholesterol, fatty acid and glucosylceramide) and aqueous material channel.  The PET™ enhancer has a strong lipid dissolving capability and can increase the drug diffusivity in the lipid channel and increase permeation around 50 to 500%. The Proven effective for pharmaceutical applications through Auxilium Pharmaceutical’s FDA-approved Testim gel, PET™ is also ideal for cosmeceutical applications as it is very effective, well tolerated and derived from natural materials.

Intercellular Drug Transport

Junginger, H.E. Visualization of Drug Transport Across Human Skin and the Influence of Penetration Enhancers. 

From permeation studies, data shows PET™ will help to deliver vitamins A and E to the dermis layer +260% and +360% respectively.

POTENTIATING EFFECT OF CPE ON VITAMINS A AND E
VITAMIN A PALMITATE/EPIDERMIS:
EFFECT OF CPE = (1.03/3.12)/0.25 = 1.32
1.3 (+30%)
VITAMIN A PALMITATE/DERMIS:
EFFECT OF CPE = (0.42/0.47)/0.25 = 3.57
3.6 (+260%)
VITAMIN E ACETATE/EPIDERMIS:
EFFECT OF CPE = (6.73/13.53)/0.25 = 1.99
2.0 (+100%)
VITAMIN E ACETATE/DERMIS:
EFFECT OF CPE = (5.14/4.57)/0.25 = 4.50
4.5 (+350%)
Kanikkannan,N et al. Structure-activity Relationship of Chemical Penetration Enhancers in Transdermal Drug Delivery. Current Med Chem 1999, 6(7): 593-605