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Microsphere size influences the foreign body reaction.

J Zandstra1, C Hiemstra, A H Petersen

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Microsphere size significantly impacts the foreign body reaction (FBR) in drug delivery. Smaller biodegradable poly-(DL-lactide-co-glycolide) (PLGA) microspheres (MSP) trigger more immune response than larger ones, influencing therapeutic outcomes.

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Area of Science:

  • Biomaterials science
  • Drug delivery systems
  • Immunology

Background:

  • Biodegradable poly-(DL-lactide-co-glycolide) (PLGA) microspheres (MSP) are used for sustained drug release.
  • The host's foreign body reaction (FBR) can affect drug release from implants.
  • Implant characteristics, including size, influence FBR.

Purpose of the Study:

  • To investigate the impact of microsphere size on the foreign body reaction (FBR).
  • To characterize FBR differences between small, large, and polydisperse PLGA MSP.

Main Methods:

  • Injected monodisperse and polydisperse PLGA MSP of varying sizes into rats.
  • Retrieved MSP implants at 7, 14, and 28 days post-transplantation.
  • Assessed FBR through macrophage infiltration, encapsulation, vascularization, and extracellular matrix deposition.

Main Results:

  • All PLGA MSP sizes showed good biocompatibility.
  • Smaller MSP (5.8 µm) were phagocytosed, unlike larger MSP (29.8 µm).
  • Increased macrophage influx, collagen deposition, and cellular infiltration were observed with smaller MSP compared to larger ones.
  • Giant cell formation occurred with large MSP but not small MSP.

Conclusions:

  • Microsphere size significantly influences the foreign body reaction.
  • FBR characteristics differ based on MSP size, impacting drug delivery efficacy.
  • Optimizing MSP size can enhance the therapeutic effectiveness of microsphere-based drug delivery systems.