Cerosomes as skin repairing agent: Mode of action studies with a model stratum corneum layer at liquid/air and liquid/solid interfaces.

The stratum corneum (SC) is the largest physical barrier of the human body. It protects against physical, chemical and biological damages, and avoids evaporation of water from the deepest skin layers. For its correct functioning, the homeostasis of the SC lipid matrix is fundamental. An alteration of the lipid matrix composition and in particular of its ceramide (CER) fraction can lead to the development of pathologies such as atopic dermatitis and psoriasis. Different studies showed that the direct replenishment of SC lipids on damaged skin had positive effects on the recovery of its barrier properties. In this work, cerosomes, i.e. liposomes composed of SC lipids, have been successfully prepared in order to investigate the mechanism of interaction with a model SC lipid matrix. The cerosomes contain CER[NP], D-CER[AP], stearic acid and cholesterol. In addition, hydrogenated soybean phospholipids have been added to one of the formulations leading to an increased stability at neutral pH. For the mode of action studies, monolayer models at the air-water interface and on solid support have been deployed. The results indicated that a strong interaction occurred between SC monolayers and the cerosomes. Since both systems were negatively charged, the driving force for the interaction must be based on the ability of CERs head groups to establish intermolecular hydrogen bonding networks that energetically prevailed against the electrostatic repulsion. This work proved for the first time the mode of action by which cerosomes exploit their function as skin barrier repairing agents on the SC.

Two- and Three-Dimensional Physical-Chemical Characterization of CER[AP]: A Study of Stereochemistry and Chain Symmetry.

The stratum corneum represents the first skin barrier against chemical and physical damage. These unique properties are based on its peculiar lipid composition with ceramides (CERs) as the main protagonists. In this study, the structural and chemical properties of the α-OH phytosphingosine [AP] CER class have been investigated. α-OH CERs are present in the stratum corneum in their d-forms; however, in most model systems the diastereomer mixture with the synthetically produced l-form is used. The d-form is well-known to form a hydrogen bonding network that helps to reduce the permeability of the lipid matrix, while the l-form does not show any hydrogen bonding network formation. In this paper, 2D (monolayers) and 3D (aqueous dispersions) models have been used to thoroughly study the physical-chemical behaviors of CER[AP] diastereomers taking into account how the symmetry of the chain pattern influences the behavior of the molecules. The chains of both diastereomers arrange in an oblique unit cell, but only the d-CER[AP] forms a supramolecular lattice (subgel phase) in both model systems. Interestingly, the chain pattern does not play any role in structure formation since the hydrogen bonding network dictates the packing properties. The 1:1 mixture of the diastereomers phase separates into two domains: one is composed of practically pure d-form and the other one is composed of a mixture of the l-form with a certain amount of d-form molecules.

Non-ionic surfactants as innovative skin penetration enhancers: insight in the mechanism of interaction with simple 2D stratum corneum model system.

Transdermal drug delivery is a passive diffusion process of an active compound through the skin which is affected by drug solubility in the multilamellar lipidic matrix of the stratum corneum (SC). Widely used non-ionic surfactants (NIS) can be added into transdermal formulations to enhance the penetration of drugs by influencing the packing of the stratum corneum lipidic matrix. Objective of our study was to analyse the interaction between selected NIS and a simple SC lipidic matrix model system using a variety of surface-sensitive techniques based on the application of Langmuir monolayers. In this work, the well-known surfactant Polysorbate 80 was compared with a modern surfactant Sucrose monolaurate. Infrared reflection-absorption spectroscopy (IRRAS) and epifluorescence microscopy provide information about the effects of those surfactants on the SC model system. Monolayer isotherms of the SC model mixture indicate a very stiff and well-packed layer, however, packing defects are evidenced in epifluorescence studies. The injection of the two NIS underneath the SC monolayers proved their potential to penetrate into the SC model at the air-water interface having a maximum insertion pressure (MIP) above the assumed lateral pressure of biological membranes. The NIS adsorbed preferentially into packing defects seen in epifluorescence microscopy studies with Sucrose monolaurate being more active than Polysorbate 80 in disordering the SC monolayer.