Long-term distribution of biodegradable microparticles in rat muscle quantified noninvasively by MRI

Jacques Kameni Tcheudji1, Catherine Cannet2, Christelle Gérard2

  • 1Novartis Institutes for BioMedical Research, Drug Metabolism and Pharmacokinetics, Basel, Switzerland.

Abstract

Insights

Magnetic resonance imaging (MRI) can track unlabeled poly(lactic-co-glycolic) acid (PLGA) microparticles in rat muscle for 28 days. This non-invasive method monitors drug delivery systems without altering their properties.

Area of Science:

  • Biomedical Engineering
  • Pharmacokinetics
  • Medical Imaging

Background:

  • Poly(lactic-co-glycolic) acid (PLGA) microparticles are widely used for controlled drug delivery.
  • Monitoring the in vivo fate of microparticles is crucial for understanding drug release kinetics and optimizing formulations.
  • Non-invasive imaging techniques are needed to track microparticles longitudinally without affecting their properties.

Purpose of the Study:

  • To assess the feasibility of using standard Magnetic Resonance Imaging (MRI) equipment to longitudinally monitor the fate of intramuscularly injected PLGA microparticles in rat muscle.
  • To validate MRI findings with histological data.

Main Methods:

  • Intramuscular injection of PLGA microparticles (SOM230 formulation) in rats.
  • Longitudinal MRI scans at various time points up to 28 days post-injection.
  • Image segmentation for quantitative analysis of MRI signals.
  • Histological analysis at selected time points for validation.

Main Results:

  • PLGA microparticles were successfully detected in vivo for up to 28 days using MRI.
  • MRI signals exhibited three distinct phases, influenced by vehicle, edema, hydration, and microparticle erosion.
  • Blood concentration peaks of SOM230 were observed at days 2 and 17, correlating with release phases.

Conclusions:

  • Standard MRI is a feasible and effective tool for longitudinal monitoring of unlabeled PLGA microparticles in muscle tissue.
  • This non-invasive approach avoids potential alterations to microparticle properties and pharmacokinetics caused by labeling.
  • The observed release patterns suggest a combination of initial compound release, diffusion, and microparticle erosion.

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