Prevention of foreign body reaction in a pre-clinical large animal model

Michail Kastellorizios, Fotios Papadimitrakopoulos, Diane J. Burgess

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

In this work, the foreign body reaction (FBR) to small subcutaneous implants was compared between small (rodent) and large (swine) animal species for the first time. Dexamethasone-releasing poly(lactic-co-glycolic acid) microspheres/polyvinyl alcohol hydrogel composite coatings were adapted to prevent FBR to small, subcutaneous implants in a large animal model (Goettingen minipigs). The implants consisted of small silicon chips (used to mimic small medical devices) that were coated with the composite formulations. The stages of the FBR were compared with previous studies in rats (that used the same-sized implants); the onset and severity of chronic inflammation (collagen deposition) was identified as a key difference between the two species. In the absence of inflammation control, fibrosis was observed from day 7 post-implantation in minipigs, whereas in rats this did not occur until day 14. This is significant as swine skin is the most commonly used model for preclinical testing of dermal formulations. It was determined that for long-term prevention of the FBR (longer than 24 h), a lag phase in dexamethasone release between days 1 and 10 did not affect the anti-FBR properties of the implant in rats. However, continuous release of dexamethasone, with no lag phase, was necessary to prevent inflammation in minipigs (effective dexamethasone dose was 100 μg delivered immediately after implantation and 10 μg/day delivered continuously thereafter). This study offers significant insight into the translation of anti-FBR strategies across species, and showcases the importance of tailoring the controlled release kinetics of the formulation to the host response.

Original languageEnglish
Pages (from-to)101-107
Number of pages7
JournalJournal of Controlled Release
Volume202
DOIs
StatePublished - 28 Mar 2015

Keywords

  • Animal models
  • Biocompatibility
  • Biosensor
  • Control drug delivery
  • Foreign body response
  • PLGA microsphere

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