We all know peptides are skincare game-changers – these tiny anti-ageing peptides can help smooth the appearance of wrinkles, firm texture, and even repair your moisture barrier (hello, benefits of peptides!). But here’s what most skincare brands don’t tell you: Many peptide formulas struggle to penetrate your skin’s natural defenses.
That’s where peptide science gets exciting. New research shows that palmitoylation (giving peptides a fatty acid “delivery boost”) helps them absorb more effectively than other methods.
So what do peptides do for your skin when delivered properly? So many things, from boosting collagen to calming irritation. This breakthrough means we’re one step closer to high-performance peptide skincare that works in harmony with your skin for visible results.
PALMITOYLATION ENHANCES SHORT POLAR PEPTIDE PERMEATION ACROSS STRATUM CORNEUM LIPID BILAYER: A MOLECULAR DYNAMICS STUDY
Choon-Peng Chng 1, Lu Zhang 2, Shikhar Gupta 2, Changjin Huang 1.
BACKGROUND
Short peptides are increasingly being explored as active ingredients in skincare products due to their potential for targeted treatment. However, delivering these peptides effectively through the skin's outermost protective layer, the stratum corneum (SC), remains a significant challenge. This is because the SC, primarily composed of a lipid matrix, acts as a formidable barrier to the penetration of many molecules. Therefore, modifications of these molecules are often needed to enhance their penetration through the skin.
OBJECTIVE
To investigate how chemical modifications, specifically cyclisation and palmitoylation, can enhance the penetration of a short polar peptide, KTTKS, across a model SC lipid bilayer using molecular dynamics (MD) simulations.
METHOD
Molecular dynamics (MD) simulations was used to investigate the interactions of a short polar peptide (KTTKS) with a model SC lipid bilayer. Three forms of KTTKS were studied:
Unmodified
Cyclised
N-palmitoylated
The simulations were used to analyse peptide adsorption onto and diffusion across the model SC lipid bilayer. The interaction energies between the peptides and the lipid bilayer, as well as the position-dependent diffusivity of the peptides was also calculated.
RESULTS
Palmitoylation significantly enhances the adsorption and diffusion of the KTTKS peptide across the SC lipid bilayer compared to the unmodified and cyclised peptides. Pal-KTTKS showed stronger binding to the SC lipid bilayer, driven by favorable interactions between its palmitic acid chain and the SC lipids. It also exhibited a higher diffusivity through the SC lipid bilayer.
CONCLUSION
This study highlights palmitoylation as a superior strategy for enhancing the delivery of short polar peptides across the SC lipid bilayer compared to cyclisation.
This is because the addition of a palmitic acid chain makes the peptide more lipophilic which facilitates its interaction with the skin's lipid matrix and allows it to better permeate the skin.
This finding has implications for the development of more effective peptide-based skincare formulations as it provides a way to enhance the delivery of these potentially beneficial molecules into the skin. By improving the penetration and possibly the efficacy of short peptides, this research could lead to the development of next-generation skincare products for various applications.
Funding information:
The study was funded by the A*STAR BMRC Strategic Positioning Fund (SPF)-A*STAR-P&G Collaboration grant (H23HW10006).
Changjin Huang reports that financial support was provided by The Procter & Gamble Company.
Author affiliations:
1 School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Republic of Singapore.
2 P&G Singapore Innovation Center (SgIC), 70 Biopolis Street, Singapore 138547, Republic of Singapore.
