To what extent are peptides absorbed through the skin when applied topically?

Topical Peptide Absorption: Limited and Highly Dependent on Delivery Method

Peptides generally do NOT penetrate the skin effectively when applied topically without specialized delivery systems, as the stratum corneum presents a formidable barrier to these hydrophilic molecules. 1

The Fundamental Barrier Problem

The primary challenge with topical peptide delivery is the skin's natural protective barrier:

• Peptides are inherently hydrophilic and typically cannot cross plasma membranes on their own, making transdermal penetration extremely limited 2
• The stratum corneum acts as the main obstacle, preventing most peptides from reaching viable skin layers where they could exert biological effects 1
• Poor membrane permeability is the most significant drawback limiting peptide delivery and effectiveness in cosmetic applications 1

Evidence for Peptide Absorption Mechanisms

When peptides do cross epithelial barriers, specific mechanisms are involved:

• Brush border peptidases in epithelial tissues actively degrade peptides before and during absorption, as demonstrated in intestinal models 3, 4
• Studies using Caco-2 cell monolayers (intestinal epithelial models) show that peptides like β-casein fragments and egg-derived peptides undergo hydrolysis by brush border enzymes immediately prior to transport across epithelial barriers 3
• Even when peptides reach epithelial surfaces, 23-36% may be degraded by surface peptidases before absorption occurs 3

Methods to Enhance Topical Peptide Delivery

Physical enhancement techniques have shown promise for improving peptide penetration:

• Thermal ablation (radiofrequency and laser) can temporarily disrupt the stratum corneum 1
• Electrical methods including electroporation and iontophoresis force peptide penetration through electrical gradients 1
• Microneedles provide mechanical disruption to create transient channels 1
• Ultrasound can enhance permeability through cavitation effects 1

Nanocarrier systems represent the most promising approach for topical peptide delivery:

• Liposomes, niosomes, and ethosomes can encapsulate peptides and facilitate skin penetration 1
• Nanoemulsions and other nanomaterials reduce skin irritation while improving product effectiveness 1
• Coupling peptides to carrier systems like liposomes or nanoparticles is necessary for intracellular uptake, as peptides cannot cross membranes independently 2

Clinical Reality vs. Marketing Claims

A critical distinction must be made between cosmetic claims and actual drug delivery:

• Most cosmetic peptide products lack the sophisticated delivery systems required for meaningful penetration 1
• Without physical enhancement or nanocarrier formulations, topical peptides remain largely on the skin surface where they are subject to degradation and washing off 1
• The peptide drug delivery literature focuses on systemic administration (injectable, oral) or specialized transdermal systems—not simple topical application 5, 6

Common Pitfalls to Avoid

• Do not assume that peptides in topical formulations automatically penetrate skin—the default is that they do not 1, 2
• Simple inclusion of peptides in creams or serums without delivery enhancement technology provides minimal to no transdermal absorption 1
• Peptide stability is compromised by surface peptidases and environmental degradation, further limiting any potential absorption 3, 4

Bottom Line for Clinical Practice

For therapeutic peptide delivery, systemic routes (subcutaneous injection, oral with specialized formulations) remain the standard because topical absorption is inadequate without advanced delivery technology 5, 6. Cosmetic peptide products may provide surface effects but should not be expected to deliver peptides to deeper skin layers or systemic circulation without incorporating physical enhancement methods or sophisticated nanocarrier systems 1.