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Stratum corneum: our skin’s protection and major challenge

The world´s demand for new and effective antimicrobial treatment for cutaneous diseases requires a deeper understanding of the structure and function of the skin's protective layer: the stratum corneum. It is also essential to learn how to deceive it when antimicrobial drugs need to be administered through the skin. Here, we will share our experience of searching for new approaches for the dermal delivery of antimicrobial drugs with the aid of nanobiotechnology.

 
How to deceive the skin barrier?
The stratum corneum is the uppermost layer of the skin and acts as a barrier to keep out contaminants and to retain moisture. It is composed of the most hydrophobic (water-fearing) lipids in nature. The more relevant are ceramides and cholesterol, forming a truly solid-like lipid structure. The skin permeability barrier function is based on this tight layer, which prevents dehydration and the entrance of microbes. However, on some occasions, this barrier function needs to be deceived for the dermal incorporation of drugs to fight parasitic and fungal skin infections.

Works developed in our laboratory clearly show that some drugs are able to penetrate and be incorporated into liquid-like artificial lipid membranes, but they are highly restricted when trying to penetrate condensed or solid-like membranes, like the ones containing high cholesterol concentration (Zulueta Díaz et al., 2016; Zulueta Díaz and Fanani, 2017). How, then, to overcome this tight lipid barrier? The most common and convenient technique is to use chemical enhancers. These additives either drag the drug molecule along with them or make changes in the structure of the stratum corneum, thereby allowing the drug molecule to penetrate the skin more easily.

Nanobiotechnology to the aid
A classical chemical enhancer is oleic acid, the more abundant lipid in oleic oil. However, ointments are not recommended for treating cutaneous disease, because of their potential for trapping excessive moisture and helping the infection to progress. Scientists are making efforts to develop water-based formulations with skin permeation enhancement properties. Among them, self-assembled nanostructures formed by a chemical derived from vitamin C (ascorbic acid) have attracted the scientist’s attention. Those molecules retain the beneficial antioxidant properties of ascorbic acid but have been modified to contain a hydrophobic tail (Fanani et al., 2017). This allows these molecules to self-organise in layers where the ascorbic end of the molecule interacts with the water while the hydrophobic side hides from it, forming lamellar arrangements.

Recent studies of our laboratory deepened into the understanding of how these molecules act on the stratum corneum lipid layer (Zulueta Díaz et al., 2019). The ascorbic acid derivatives incorporate into the skin lipids and increase the elasticity of the stratum corneum making it more liquid-like. Additionally, they enlarge the thinner, more fluid part of the layering structure at the nanoscale. This leads to a path that would penetrate the stratum corneum layer by layer, where a drug molecule may find an easier way to travel along the skin.

Our interest in the ascorbic acid derivatives also resides in its capacity to be a solvent for some well-known and effective antimicrobial drugs, such as Amphotericin B. This drug has been generally consumed for fifty years but its insolubility in water makes it difficult to use for dermal treatment. The self-assembled nanostructures formed by the ascorbic acid derivatives have the potential to host such antimicrobial drugs into their hydrophobic structure, accommodating the drugs among the hydrophobic tails, and still be effective in a water-based formulation.

The development of efficient dermal treatment for cutaneous parasitosis is particularly relevant in tropical regions where cutaneous leishmaniasis has become a so-called neglected disease. This zoonosis (a disease spread through animals) has raised little interest from the pharmaceutic industry and therefore needs the attention of public health authorities and the scientific community. Our approach focuses on the development of new treatments for this and other cutaneous diseases, with the aid of this new and promising branch of science, nanobiotechnology.

Team members: Dr Yenisleidy de las Mercedes Zulueta Díaz, Dr Natalia E. Nocelli and Dr Raquel V. Vico.

References

Fanani, M.L., Vico, R.V., Benedini, L., 2017. Alkyl esters of L-ascorbic acid: From synthesis to applications, in: Parsons, E. (Ed.), Ascorbic Acid: Properties, Synthesis and Applications. Nova Science Publishers, Inc., pp. 141–174.
Zulueta Díaz, Y. de las M., Fanani, M.L., 2017. Crossregulation between the insertion of Hexadecylphosphocholine (miltefosine) into lipid membranes and their rheology and lateral structure. Biochim. Biophys. Acta - Biomembr. 1859, 1891–1899. https://doi.org/10.1016/j.bbamem.2017.06.008
Zulueta Díaz, Y. de las M., Menghi, K., Guerrero, M.L., Nocelli, N., Fanani, M.L., 2019. L-ascorbic acid alkyl esters action on stratum corneum model membranes: an insight into the mechanism for enhanced skin permeation. Colloids Surfaces B Biointerfaces 110621. https://doi.org/10.1016/j.colsurfb.2019.110621
Zulueta Díaz, Y. de las M., Mottola, M., Vico, R. V, Wilke, N., Fanani, M.L., 2016. The Rheological Properties of Lipid Monolayers Modulate the Incorporation of L-Ascorbic Acid Alkyl Esters. Langmuir 32, 587–595. https://doi.org/10.1021/acs.langmuir.5b04175

Written By

Maria Laura Fanani
Universidad Nacional de Córdoba - CONICET

Contact Details

Email: lfanani@fcq.unc.edu.ar
Telephone:
++543512015184

Address:
Departamento de Quimica Biologica Ranwel Caputto, Facultad de Ciencias Quimicas - UNC
Centro de Investigaciones en Quimica Biologica de Cordoba- CONICET
Haya de la Torre y Medina Allende
Cordoba City
CORDOBA
ARGENTINA
X5000HUA

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