Amino Acid-Based Transdermal Penetration Enhancers

Abstract

Transdermal drug delivery offers an attractive alternative to conventional routes of drug administration. However, development of transdermal patches for drugs with a molecular mass larger than 500 Da is hindered primarily by low skin permeability. One of the approaches to increase drug flux through the skin into systemic circulation is the use of transdermal permeation enhancers, also known as penetration enhancers, percutaneous absorption promoters, or accelerants. Amino acid derivatives seem to be a promising class of permeation enhancers, especially those with a hydrophobic “tail” attached to an amino acid “head” via a biodegradable linkage, e.g., an ester bond. Such an amphiphilic enhancer could be incorporated into the stratum corneum lipid barrier and disrupt the tight arrangement of the membrane lipids. After reaching the enzymatically active nucleated epidermis, its labile bond could be hydrolyzed, thus releasing known nontoxic compounds with much lower irritation potential. In this chapter, we present an overview of acyclic amino acid-based permeation enhancers including derivatives of glycine (e.g., DDAA), alanine (e.g., DDAIP), sarcosine (e.g., lauroylsarcosine), proline (e.g., dodecyl N-acetylprolinate), and 6-aminohexanoates (T12 and DDAK).