A critical element in many therapies is the ability to penetrate thick tissues to reach as many of his cells as possible. Tissue penetration is critical in solid tumour treatment as well as an enabling factor in topical delivery such as transdermal and buccal delivery. We have been tackling this challenge in two fashion designing ultra-flexible polymersomes that can translocate across pores considerably smaller than their diameter and by analysing their diffusion across the interstitial space within the tissue.
This is high complex and interconnected space with many possible paths whose probability of occupancy can be estimated by percolation theories. Here a non-trivial effect is the so-called size-exclusion enhancement diffusion where larger objects diffuse more rapidly across porous systems than smaller ones as they can access a considerably limited number of paths and hence reach larger distance in shorter times. We have observed such an effect using polymersomes in different models including tight tissue such as skin and oral mucosa. More recently, in collaboration with Tambet Teesalu at Tartu University and Erkki Ruoslahti at the Sanford-Burnham Medical Research Institute, we have applied this to intraperitoneal administration demonstrating that polymersomes can penetrate and reach more effectively peritoneal metastasis.
- L. Simón-Gracia, H. Hunt, P. Scodeller, J. Gaitzsch, V. R. Kotamraju, K. N. Sugahara, O. Tammik, E. Ruoslahti, G. Battaglia, and T. Teesalu iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes Biomaterials 2016, 104, 247–257
- L. Simón-Gracia, H. Hunt, P. Scodeller, J. Gaitzsch, G. B. Braun, A. A. Willmore, E. Ruoslahti, G. Battaglia, and T. Teesalu Paclitaxel-loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy Mol. Cancer Ther. 2016, 15, 670-679
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- V. Hearnden, S. MacNeil, G. Battaglia*. Tracking Nanoparticles in Three-Dimensional Tissue Engineered Models Using Confocal Laser Scanning Microscopy Meth. Mol. Biol. 2011, 695, 41-51
- V. Hearnden, H. Lomas, S. MacNeil, M. Thornhill, C. Murdoch, A. Lewis, J. Madsen, A. Blanazs, S.P. Armes, and G. Battaglia Diffusion studies of nanometer polymersomes across tissue engineered human oral mucosa Pharm. Res. 2009, 26 (7), 1718-1728