Novel iron oxide microparticles used to render stone fragments paramagnetic: assessment of toxicity in a murine model

Abstract

Purpose: We developed novel peptide coated iron oxide supraparamagnetic microparticles that bind to calcium stones, allowing for extraction of these stones with magnetic tools. Urothelial and fibroblast cell lines show minimal to no toxicity when exposed to the particles. Before clinical evaluation, assessment of the in vivo systemic toxicity of the microparticles was required. This was studied in a murine model.

Materials and methods: A total of 64 mice were exposed to different concentrations of microparticles (0.5, 1 or 5 mg/dl) intravesically or intravenously via the tail vein. Mice were sacrificed at different intervals (days 1, 3, 28 and 84). Representative samples from the brain, lung, heart, kidney and liver were evaluated histologically at each time point. The tissue distribution pattern of the particles and any degree of inflammation was noted by a clinical pathologist. Liver function tests were also performed at similar intervals.

Results: All mice survived until the assigned end point and appeared healthy after exposure to microparticles. In the bladder installation group no particles were seen in any organ regardless of the particle concentration instilled. In the intravenous instillation group there was tissue distribution in the liver and to a lesser extent in the lung. There was mild inflammation in the liver and lung, which was dose dependent.

Conclusions: Novel iron oxide supraparamagnetic microparticles used to render stone fragments paramagnetic in the urinary collecting system did not appear to cross intact urothelial membranes. When introduced systemically, they led to minimal inflammatory changes, predominantly in the liver and lung. Additional long-term studies are required.