Synthetic, implantable, biodegradable polymers for controlled release of radiosensitizers

Introduction: Synthetic implantable, biodegradable polymers offer the susta ined focal release of disparate therapeutic agents for the treatment of hum an malignant brain rumors. The role of polymeric devices for the local deli very of radiosensitizers remains unexplored however We therefore quantified the release of the representative radiosensitizers IUdR (5-iodo-2'-deoxyur idine), tirapazamine (3-amino-1,2,4-benzotriazine-1, 4-dioxide) and etanida zole [N-(2-hydroxyethyl)-2-nitro-1-imidazole-1-acetamide] from the [(poly(b is(p-carboxyphenoxyl-propane) (PCPP):sebacic acid (SA) (PCPP:SA ratio 20:80 )] polymer. Methods: For measurements of controlled release, triplicate polymer discs w ere incubated for known intervals in 2 mi 0.1 phosphate-buffered saline, pH 7.4, 37 degrees C. Using a predefined schedule, the supernatant fractions were systematically removed and replaced with fresh solution. The supernata nt fractions were measured The cumulative percentage of the loaded drug tha t appeared in these serial supernatant fractions was plotted vs. time. The percentage of the drug that was loaded into each polymer and that was relea sed vs. time was fit to the power function of the form y = (a) *t(b), where y is the cumulative released agent, a and b are constants and t is time (d ays). Results: The IUdR was released over an interval of approximately one week, while the release of the tirapazimine persisted for over 100 days. The etan idazole was released most rapidly, over a period of hours. Modeling of rele ase showed that regardless of percentage loading of the drug the monoexpone ntial function showed high correlation of the fit of the plot of the releas e vs, time. Conclusions: These results suggest that the hydrophilicity and percentage loading of the drug predominantly determine the rate of release. Based upon these results, IUdR and tirapazamine warrant preclinical testin g for radiosensitization of human malignant brain rumors via the synthetic implantabte, biodegradable polymeric devices.