Clinical Relevance of Topical Active Delivery Systems in Cosmetics

By: Haw-Yueh Thong, MD, MS, Dnational Taiwan University Hospital and Howard I. Maibach, MD, University of California

Posted: May 4, 2009, from the May 2009 issue of Cosmetics & Toiletries.

Depending on a drug or cosmetic ingredient’s intended target, topical delivery systems are broadly categorized as either transdermal drug or dermal drug/cosmetic.¹ Transdermal drug delivery (TDD) is the controlled release of drugs through intact skin to obtain therapeutic levels systematically and to affect specified targets for specific purposes such as contraception, among others. Dermal drug/active cosmetic ingredient delivery (DDD) is similar to TDD except that the specified target is the skin itself.^1,2 Cosmetic ingredients, including those for antiaging, known as cosmeceuticals, presumably may have the same site of action. The cosmetic and/or transdermal route is indeed desirable by the industry but the success of DDD and cosmetic active ingredient delivery (CAID) technologies remains limited and faces many challenges, one of which is low skin permeability that hinders the development of DDD/CAID for macromolecules.

Overcoming the skin barrier safely and reversibly while enabling percutaneous absorption is a fundamental problem in the field of CAID, TDD and DDD. Advances have been made in recent decades to overcome skin barrier properties,3,4 including physical means such as iontophoresis, sonophoresis and microneedles; chemical means using penetration enhancers; and biochemical means such as liposomal vesicles and enzyme inhibition. A rich library of textbook literature summarizes these extensive experimental backgrounds—largely within the last half of the 20th century.^5,6

CAID Systems
CAID systems are capable of delivering localized effects while minimizing systemic side effects and they are the primary modalities for dermatologic treatment or cosmetic purposes. Examples include topical antiaging products, photo-protective materials, cosmetics and moisturizers. Many cosmetic formulations use chemical penetration enhancers to overcome the skin barrier. Again, percutaneous absorption remains a key issue to the success of CAID technology.

As a model for CAID, delivery systems of topical corticosteroids and their pharmacokinetic/pharmacodynamic relationships have been studied extensively as aids to optimizing topical treatment.^7-9 For instance, the correlation between the bioavailability of topical corticoids and the thermodynamic activity of the medicament in different bases have been studied.^{10, 11} Unfortunately few such in vivo human studies have been performed for active cosmetic ingredients.

In a similar investigation, Leopold and Maibach12 characterized local anesthetics pharmacodynamically by measuring thermal thresholds over time with a thermal sensory analyzer (TSA) in human subjects. The results showed that the local anesthetics investigated affect thermal thresholds to a different extent, and that linear relationships exist between cold sensation parameters and the solubility of the local anesthetic bases in medium chain triglycerides and with the drug flux at 50% saturation.