Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously-injected polymeric microsphere suspension formulations

Claire Patterson, Dean Murphy, Sarah Irvine, Leigh Connor, Zahra Rattray

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Abstract

Purpose: Subcutaneously or intramuscularly administered biodegradable microsphere formulations have been successfully exploited in the management of chronic conditions for over two decades, yet mechanistic understanding of the impact of formulation attributes on in vivo absorption rate from such systems is still in its infancy.

Methods:
Suspension formulation physicochemical attributes may impact particulate deposition in subcutaneous (s.c.) tissue. Hence, the utility of synchrotron X-ray microcomputed tomography (μCT) for assessment of spatial distribution of suspension formulation components (PLG microspheres and vehicle) was evaluated in a porcine s.c. tissue model. Optical imaging of dyed vehicle and subsequent microscopic assessment of microsphere deposition was performed in parallel to compare the two approaches.
Results: Our findings demonstrate that synchrotron μCT can be applied to the
assessment of microsphere and vehicle distribution in s.c. tissue, and that
microspheres can also be visualised in the absence of contrast agent using this
approach. The technique was deemed superior to optical imaging of macrotomy for the characterisation of microsphere deposition owing to its non-invasive nature and relatively rapid data acquisition time.
Conclusions: The μCT method outlined in this study provides a novel insight into the relative distribution of vehicle and suspended PLG microspheres following s.c. injection. A potential application for our findings is understanding the impact of injection, device and formulation variables on initial and temporal depot geometry in pre-clinical or ex-vivo models that can inform product design.
Original languageEnglish
Article number97
Number of pages11
JournalPharmaceutical Research
Volume37
Issue number6
DOIs
Publication statusPublished - 14 May 2020

Keywords

  • X-ray computed tomography
  • subcutaneous injection
  • microsphere
  • depot
  • imaging

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