Delivery of small hydrophilic molecules across the stratum corneum: Identification of model systems and parameters to study topical delivery of free amino acids

Abstract

Free amino acids (FAAs) constitute the largest component (∼40 %) of the so-called natural moisturizing factors of the skin. Their level declines in dry skin conditions and one strategy to overcome this problem may involve the topical delivery of FAAs through appropriate strategy. The objective of the present study was therefore to identify alternative skin models and study the corneocyte-water partition coefficients (K_COR/W) and permeation coefficient (K_P) of 18 FAAs. The K_COR/W was studied using standard protocols and the permeation studies were conducted using Franz diffusion cell. The results indicate that the FAAs have high partitioning behavior to the corneocytes. The K_COR/W values of the human COR and that of pig ear skin were better correlated with each other than that of keratin isolated from chicken feathers. The presence of lipid in the stratum corneum (SC), initial concentration of the FAAs, and permeation enhancers affect the K_COR/W. The FAAs have low permeation into the SC which suggests the need for permeation enhancers in designing dosage form containing these compounds. Even though the investigated mathematical models show good prediction of the Kp values, better prediction could be obtained by considering factors such as the possible entrapment of the FAAs by the CORs.