Nanoparticle Skin Penetration: Depths and Routes Modeled In-Silico.

Summary

A literature-derived in-silico skin model with 19 parameters achieved 95% predictive accuracy and pinpointed hair follicle diameter as the dominant determinant of nanoparticle penetration. Vehicles strongly shape routes: emulsions/oil favor intercellular and transappendageal pathways, whereas aqueous media favor intracellular transport.

Key Findings

• In-silico model integrating 19 parameters achieved 95% predictive accuracy for nanoparticle skin penetration.
• Hair follicle diameter emerged as the most influential factor governing penetration depth and routes.
• Vehicle effects: emulsions/oils promote intercellular and transappendageal routes; aqueous media favor intracellular transport.
• Pig and rabbit skin are the most suitable preclinical models to simulate human skin for NP penetration.

Clinical Implications

Formulators can tailor nanoparticle size and vehicle to leverage follicular pathways and optimize delivery to target skin layers while improving safety by predicting systemic exposure risks.

Limitations

• Relies on heterogeneous literature data; external prospective validation on standardized datasets is needed
• Model interpretability and code/data availability were not detailed in the abstract

Future Directions

Prospective validation against harmonized in vivo/ex vivo datasets; integrate mechanistic diffusion/appendage models; open-source tool deployment for cosmetic formulation design.