Biodistribution of fluorescence-labelled EGF protein from slow release NanoZolid depots in mouse

Int J Pharm. 2021 May 15:601:120588. doi: 10.1016/j.ijpharm.2021.120588. Epub 2021 Apr 15.

Abstract

Aim: The study was designed to evaluate the ability of the calcium sulfate based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity.

Methods: NanoZolid-formulated EGF protein labelled with a near infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 h post administration, utilizing whole body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling.

Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression.

Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g. receptor binding capability. This may have a good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: Bioresorbable; Calcium sulfate; Controlled release; EGF; IRDye 800CW; NanoZolid.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Epidermal Growth Factor*
  • Fluorescence
  • Mice
  • Mice, Nude
  • Tissue Distribution

Substances

  • Epidermal Growth Factor