Translocation of flexible polymersomes across pores at the nanoscale

Carla Pegoraro; Denis Cecchin; Jeppe Madsen; Nicholas Warren; Steven P Armes; Sheila MacNeil; Andrew Lewis; Giuseppe Battaglia

doi:10.1039/c3bm60294j

Translocation of flexible polymersomes across pores at the nanoscale

Biomater Sci. 2014 Apr 1;2(5):680-92. doi: 10.1039/c3bm60294j.

Authors

Carla Pegoraro¹, Denis Cecchin², Jeppe Madsen³, Nicholas Warren⁴, Steven P Armes⁴, Sheila MacNeil⁵, Andrew Lewis⁶, Giuseppe Battaglia⁷

Affiliations

¹ Department of Biomedical Sciences, University of Sheffield, Sheffield, UK and The Kroto Research Institute, University of Sheffield, Sheffield, UK and Department of Material Science and Engineering, University of Sheffield, Sheffield, UK.
² Department of Chemistry, University College London, London, UK and The MRC/UCL Centre for Medical Molecular Virology, University College London, London, UK. g.battaglia@ucl.ac.uk and Biocompatibles UK Ltd, Farnham, UK.
³ Department of Biomedical Sciences, University of Sheffield, Sheffield, UK and Department of Chemistry, University of Sheffield, Sheffield, UK.
⁴ Department of Chemistry, University of Sheffield, Sheffield, UK.
⁵ The Kroto Research Institute, University of Sheffield, Sheffield, UK and Department of Material Science and Engineering, University of Sheffield, Sheffield, UK.
⁶ Biocompatibles UK Ltd, Farnham, UK.
⁷ Department of Chemistry, University of Sheffield, Sheffield, UK and Department of Chemistry, University College London, London, UK and The MRC/UCL Centre for Medical Molecular Virology, University College London, London, UK. g.battaglia@ucl.ac.uk.

PMID: 26828800
DOI: 10.1039/c3bm60294j

Abstract

Hierarchical biological systems such as tissues and organs are often characterised by highly crowded and packed environments with nanoscopic interconnections between them. Engineering nanovectors that can penetrate and diffuse across these is critical to ensure enhanced delivery and targeting. Here we demonstrate that flexible polymeric vesicles, known as polymersomes, enable the translocation of large macromolecules across both synthetic and biological porous systems. We compare the translocation across narrow pores of different polymersome formulations. We demonstrate that effective translocation depends on the right combination of mechanical properties and surface lubrication. We prove that with the effect of external gradients (e.g. osmotic pressure, capillarity, hydration, etc.) polymersomes can translocate across pores with diameters one order of magnitude smaller without breaking. We demonstrate that these properties are essential to develop effective tissue penetration and show polymersome mediated transdermal delivery of large macromolecules such as dextran and antibodies using human ex vivo skin.