3:09 PM Abstract No. 372 In vitro evaluation of irinotecan loaded bioresorbable microspheres for arterial chemoembolization

Abstract

To evaluate the potential of the drug loadable resorbable microspheres (BRMS) as platforms for irinotecan delivery in arterial chemoembolization. BRMS were prepared from carboxymethyl cellulose and chitosan by using an inverse emulsion method. The degradability of these microspheres in 10 μg/mL lysozyme at 37°C was determined by gravimetry. Drug loading was performed by immersing 100-300 μm BRMS in an irinotecan hydrochloride solution (20 mg/mL) for 2 h. Drug loading efficiency was determined by measuring the irinotecan concentration remaining in the loading solution with a spectrophotometer at 369 nm. The drug distribution inside the microspheres was determined with multiphoton confocal fluorescent microscopy. Release experiments were performed in distilled water (DI), saline (0.9% NaCl, pH = 5.6) and 0.01 M phosphate buffered saline (PBS, pH = 7.4 and pH = 5.5) under static medium conditions. The suspendability of the drug loaded BRMS was tested in water/contrast agent mixtures in different ratios, and then the injectability was tested with microcatheters (ID = 0.021” and 0.027”). The dry weight of the BRMS showed a consistent decrease over the period of incubation in a 10 μg/mL lysozyme solution with 39.1% mass remaining on day 21. Irinotecan was loaded efficiently onto the 100-300 μm BRMS with a loading percentage of 90.67% and an average of 14% decrease in the microsphere size at 2 h. Confocal imaging revealed an even distribution of irinotecan throughout the BRMS. In different releasing media, drug loaded BRMS released irinotecan at different rates depending on the ion concentration. At 2 h, the percentage of drug released were 12.7 ± 3.0%, 98.1 ± 2.7%, 99.4 ± 1.0%, and 100.0 ± 0.0% for 100-300 μm BRMS in DI, saline, PBS (pH = 7.4) and PBS (pH = 5.5), respectively. Drug loaded BRMS formed a stable suspension in a 7:3 water/contrast mixture, which could be easily injected through microcatheters without aggregating or clogging. BRMS are promising as carriers for irinotecan delivery in arterial chemoembolization.