Drug diffusion in biomimetic hydrogels: importance for drug transport and delivery in non-vascular tumor tissue

Eur J Pharm Sci. 2022 May 1:172:106150. doi: 10.1016/j.ejps.2022.106150. Epub 2022 Feb 26.

Abstract

Hydrogels of varying complexity are routinely used as scaffolds and 3D structures for in vitro tumor models to increase physiological relevance within pre-clinical cancer research. Relatively simple hydrogels such as agarose are well characterised, meanwhile biomimetic gels containing collagen and fibrin(ogen) have been studied to a much lesser extent. In this study, hydrogels mimicking the biophysical characteristics of liver cancer progression were investigated in terms of their UV-properties and influence on diffusion coefficients of different substances. UV-imaging technology was used to both visualize and quantify the diffusion process in a simple and rapid way. In general, agarose gel diffusion agreed well with predictions using the Stokes-Einstein equation meanwhile the biomimetic gels reduced diffusion coefficients by up to 70%. For doxorubicin, spatio-temporal tissue concentration modelling was used to translate in vitro diffusion to the more clinical context of tumor penetration in a solid liver tumor supplied by arterial blood.

Keywords: UV-imaging; doxorubicin; extracellular matrix; hydrogels; liver cancer; tumor diffusion.

MeSH terms

  • Biomimetics
  • Collagen / chemistry
  • Diffusion
  • Humans
  • Hydrogels* / chemistry
  • Neoplasms*
  • Sepharose / chemistry

Substances

  • Hydrogels
  • Collagen
  • Sepharose