Enhancing Human Skin Penetration with Biodegradable Enzymatic Nanomotors

ACS Nano, vol. 20, pp. 23013–23033

Abstract

The skin is the body's primary biological barrier, largely due to the highly organized structure of the stratum corneum (SC). Although essential for protection, this barrier function limits the efficacy of transdermal drug delivery, as most topically applied compounds fail to reach deeper skin layers at therapeutically relevant concentrations. Existing approaches often rely on physical disruption of the barrier, which can cause undesirable side effects. Moreover, many prior studies have been conducted in murine models, which do not accurately recapitulate human skin physiology, hindering the translation to humans. Here, we present an alternative approach using enzymatically powered nanomotors tested in a human reconstructed skin model. We developed organic nanomotors composed of poly(lactic-co-glycolic acid) functionalized with urease, and we proved their biocompatibility and degradability. Our results show that nanomotors penetrate the skin with 15.7% efficacy, 2.5 times more than passive nanoparticle controls. This enhanced penetration is attributed to their active motion and their ability to induce alterations in the lipid organization of the SC, an effect confirmed by synchrotron radiation small-angle X-ray scattering and electron microscopy. These findings highlight the potential of enzymatic nanomotors as a nondisruptive and effective platform for future transdermal delivery in human skin, combining advantages of both chemical enhancers and nanoparticles.

Authors 9

1. Carles Prado-Morales

   Universitat de Barcelona · Barcelona Institute of Science and Technology · Institute for Bioengineering of Catalonia

   Affiliation as printed

   Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , ,

   Universitat de Barcelona, Doctorate in Biotechnology, Facultat de Farmàcia i Ciències de l’Alimentació , ,

2. Taco Waaijman

   Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Amsterdam UMC, Location VUMC , , ,

3. Ines Macías-Tarrío

   Universitat de Barcelona · Barcelona Institute of Science and Technology · Institute for Bioengineering of Catalonia

   Affiliation as printed

   Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , ,

   Universitat de Barcelona , , ,

   Universitat de Barcelona, Doctorate in Biotechnology, Facultat de Farmàcia i Ciències de l’Alimentació , ,

4. Cristián Huck‐Iriart

   ALBA Synchrotron (Spain)

   Affiliation as printed

   ALBA Synchrotron Light Source, Cerdanyola del Vallès , ,

5. Tiziana Russo

   Universitat de Barcelona · Barcelona Institute of Science and Technology · Institute for Bioengineering of Catalonia

   Affiliation as printed

   Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , ,

   Universitat de Barcelona, Facultat de Biologia , ,

6. Joël Gálvez-Savoca

   Barcelona Institute of Science and Technology · Institute for Bioengineering of Catalonia

   Affiliation as printed

   Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , ,

7. César Rodriguez‐Emmenegger Aachen DWI - Leibniz Institute for Interactive Materials

   DWI – Leibniz Institute for Interactive Materials · Institució Catalana de Recerca i Estudis Avançats · Barcelona Institute of Science and Technology · Institute for Bioengineering of Catalonia

   Affiliation as printed

   DWI − Leibniz Institute for Interactive Materials , ,

   Institució Catalana de Recerca i Estudis Avaņats (ICREA) , ,

   Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , ,

8. Jasper J. Koning

   Amsterdam UMC Location Vrije Universiteit Amsterdam · Amsterdam institute for Immunology and Infectious Diseases

   Affiliation as printed

   Amsterdam UMC, Location VUMC , , ,

   Amsterdam institute for Immunology and Infectious diseases, Inflammatory diseases , ,

9. Samuel Sánchez

   Institució Catalana de Recerca i Estudis Avançats · Barcelona Institute of Science and Technology · Institute for Bioengineering of Catalonia

   Affiliation as printed

   Institució Catalana de Recerca i Estudis Avaņats (ICREA) , ,

   Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST) , ,