In Vitro Stability of Tris-acryl Gelatin Microspheres in a Multipharmaceutical Chemoembolization Solution

Abstract

To evaluate the in vitro stability of tris-acryl gelatin microspheres (TAGMs) in a multipharmaceutical solution as a preliminary step before planned hepatic chemoembolization with TAGMs. Half-cm(3) aliquots of 100-300- micro m and 300-500- micro m TAGMs were suspended in 1 mL of normal saline solution (NSS), 1 mL of ethiodized oil, or 1 mL of a standard chemoembolization solution (cisplatin 100 mg, doxorubicin 50 mg, mitomycin 10 mg, ethiodized oil 3 mL, and iodixanol 5 mL). Mixtures were incubated at 37 degrees C for 24 hours and were then examined visually and with use of light microscopy. Solutions containing ethiodized oil required centrifugation for separation. Determination of average sphere diameter after 24-hour chemoembolization incubation was performed after washing in ethanol, washing in acetone, and rinsing in 0.9% aqueous sodium chloride solution. TAGMs in NSS had no gross degradation, were intact on light microscopy, and had no visually perceptible change in average diameter. TAGMs in ethiodized oil alone appeared to dissolve into a cloudy solution; however, centrifugation separated spheres from ethiodized oil as a layer, which was intact on light microscopy. Spheres incubated in the chemoembolization solution were not grossly visible as a result of the deep red color of doxorubicin (which stained the spheres), but were easily seen after centrifugation. There were similar numbers of spheres per field on microscopy with a minimal (but significant) increase in analyzed diameter. TAGMs are stable in a standard chemoembolization solution and may be suitable as a substitute for PVA particles in hepatic chemoembolization.