In the personal care and pharmaceutical industry, formulators of transdermal or topical formulations often strive to optimise the interactions, absorption and permeation of active ingredients with and into the skin. For instance, in sunscreen formulations, the active ingredient needs to reside on the skin’s surface to provide adequate UV protection. On the other hand, for pharmaceutical transdermal formulation, permeation and absorption into the body system is vital for the drug to be efficacious.

The current state-of-the-art methods to evaluate the penetration of ingredients through skin involves experimental investigations that are either inaccurate or elicits ethical concerns.  To overcome the drawbacks of current skin penetration methods, scientists at A*STAR have come together to create a computational method for investigating skin penetration.

SKINSilico is a simulation platform that allows formulators to simulate and visualise active ingredients’ permeation through the lipid lamellar structures between skin cells at an atomistic scale. Using molecular diffusion as input, we can solve large-scale diffusion equations and predict the amount of ingredients penetrating through the barrier layer into the deeper layers of skin.  

To further investigate for a complete picture of systemic absorption, IHPC will be working with the Skin Research Institute of Singapore (SRIS) to understand how the body system response to the penetration of active ingredients in an accurate and safe manner. The A*STAR-affiliated researchers also include the Singapore Institute of Food and Biotechnology Innovation (SIFBI) in phase two of the project.

Features

• Realistic skin lipid structure at the barrier layer
• Coupling molecular simulations output with numerical diffusion model to achieve realistic scale penetration understanding
• Integration skin permeation data to systemic uptake model from SRIS/SIFBI

The Science Behind

IHPC uses all atoms molecular dynamics simulations on a realistic splayed lipids model to compute the diffusion and partition coefficient of chemical actives through the intercellular routes at the barrier layer (Fig 1.). These parameters are fed into a numerical model on a finite volume grid to compute the quantity of active penetration at a certain depth over a given period of time. The team then extends the numerical model of diffusion into the dermis^[1] and subcutis^[2] region and integrates SKINSilico to the systemic uptake model from SRIS and SIFBI. 

Fig 1. An Illustration of diffusion through the skin barrier layer via the intercellular lipid route

Acknowledgment

The provision of computing facilities by A*STAR Computational Resource Centre in Singapore, the National Supercomputing Centre of Singapore (NSCC), as well as the financial support from the Agency for Science, Technology and Research (A*STAR) for a RIE2020 Advanced Manufacturing and Engineering (“AME”) IAF-PP “Specialty Chemicals Programme” grant (Project Reference: A1786a0028).

Industry Applications

SKINSilico can be applied in the following sectors to understand and predict the penetration of active ingredients into the skin:

• Consumer products
• Cosmetics
• Transdermal formulations

For more info or collaboration opportunities, please write to enquiry@ihpc.a-star.edu.sg.

Glossary

• ^[1] Dermis: The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain.
• ^[2] Subcutis: The subcutis is the deepest layer of the integument, sandwiched between the dermis and skeletal muscle.