Novel Stone-Magnetizing Microparticles: In Vitro Toxicity and Biologic Functionality Analysis

Abstract

We have developed novel iron-based microparticles (Fe-MP) that bind to calcium oxalate stone fragments, rendering them paramagnetic. Previously, we demonstrated enhanced efficiency of stone extraction in an inanimate model using magnetic instrumentation. Before in vivo stone extraction studies, we sought to further characterize Fe-MP with regard to cellular toxicity and to assess the influence of biologic fluids on binding performance. Monolayers of murine fibroblasts, human urothelium, and human transitional-cell carcinoma cells were exposed to 1 mg/mL of Fe-MP or saline via an agarose overlay. Cellular viability was assessed using neutral red staining and densitometry. Biologic functionality: Human calcium oxalate stone fragments were incubated with a solution of 1 mg/mL of Fe-MP containing varying concentrations of urine (10%-50%) or blood (0.5%-2%) for 10 minutes. Fragments were then extracted using an 8F magnetic tool. Assays of 10 stone fragments categorized as small (3-3.9 mg) or large (6-6.9 mg) were run in quadruplicate at each concentration. No toxicity was seen in any of the three cell lines after 48 hours of particle exposure, except in urothelial cells at the lowest cell concentration. Stone extraction success was 100% for all stones, regardless of concentration of urine or blood, and extractions were completed in less than 10 minutes. Preliminary toxicity testing revealed minimal to no cellular toxicity that was attributable to Fe-MP. The microparticles function well in the presence of clinically relevant concentrations of urine and blood that may be present during endoscopic stone surgery. Further toxicity and stone extraction testing in animal models is necessary.