Jacques Kameni Tcheudji1, Catherine Cannet2, Christelle Gérard2, Catherine Curdy3, Nicolau Beckmann2. 1. Novartis Institutes for BioMedical Research, Drug Metabolism and Pharmacokinetics, Basel, Switzerland. 2. Novartis Institutes for BioMedical Research, Analytical Sciences & Imaging, Basel, Switzerland. 3. Novartis Institutes for BioMedical Research, Novartis Pharma Development, Basel, Switzerland.
Abstract
PURPOSE: To demonstrate the feasibility of MRI to monitor longitudinally the fate of PLGA microparticles in muscle tissue after intramuscular injection in rats using standard equipment. METHODS: MRI was performed at different time points and until day 28 after intramuscular administration of microparticles. Image segmentation was used to quantify the MRI signals. Histology was performed at selected time points to validate the in vivo observations. The SOM230-long acting release formulation was used as test compound. RESULTS: Microparticles were detected in vivo until 28 days following their administration. Imaging and histology data indicated that the MRI signals followed three phases: in an early phase (≤ 48 h after injection), vehicle, edema and hydration of microparticles contributed to the signals. In the second (days 3-17) and third phases (day 17 onward), microparticle hydration was the main contributor. SOM230 in blood displayed peaks at days 2 and 17. CONCLUSION: MRI was suitable to follow longitudinally the presence of PLGA microparticles in the rat muscle without labeling them. This is advantageous, because labeling could potentially alter the properties and pharmacokinetics of the microparticles. Data were consistent with an initial compound release followed by diffusion and microparticle erosion as main mechanisms of SOM230 release.
PURPOSE: To demonstrate the feasibility of MRI to monitor longitudinally the fate of PLGA microparticles in muscle tissue after intramuscular injection in rats using standard equipment. METHODS: MRI was performed at different time points and until day 28 after intramuscular administration of microparticles. Image segmentation was used to quantify the MRI signals. Histology was performed at selected time points to validate the in vivo observations. The SOM230-long acting release formulation was used as test compound. RESULTS: Microparticles were detected in vivo until 28 days following their administration. Imaging and histology data indicated that the MRI signals followed three phases: in an early phase (≤ 48 h after injection), vehicle, edema and hydration of microparticles contributed to the signals. In the second (days 3-17) and third phases (day 17 onward), microparticle hydration was the main contributor. SOM230 in blood displayed peaks at days 2 and 17. CONCLUSION: MRI was suitable to follow longitudinally the presence of PLGA microparticles in the rat muscle without labeling them. This is advantageous, because labeling could potentially alter the properties and pharmacokinetics of the microparticles. Data were consistent with an initial compound release followed by diffusion and microparticle erosion as main mechanisms of SOM230 release.