Controlled Release of BCNU from Locally Implanted Polymeric Wafer for the Treatment of Brain Tumor

다국어 초록 (Multilingual Abstract)

The localized delivery of anticancer agents using polymeric implants is an alternative to the systemic administration for the treatment of malignant glioma. The purpose in the present study was to develop an implantable polymeric device, which can release intact BCNU for short-term period from day 4 to day 7 depending on drug loading amount, and to evaluate its in vitro anti-tumor activity against XF 498 human CNS tumor cells and in vivo anti-tumor activity against tumor-bearing animal model of L1210 mouse leukemia cells with the parameter of mean survival time of animals. In vitro release of BCNU in pH 7.4 phosphate buffered saline (PBS) was prolonged up to 1 week after initial burst release. Anti-tumor activity of BCNU-loaded poly(D,L-lactide-co-glycolide) (PLGA) wafer against XF 498 human CNS tumor cells continued over 10 days and, PLGA only did not affect the growth of the cells. Meanwhile, the cytotoxicity of BCNU powder disappeared within 12 h. For in vivo anti-tumor activity of BCNU-loaded PLGA wafer against tumor-bearing animal model of L1210 mouse leukemia cells, the interstitial release of BCNU implanted in the flank of mice resulted in 5-fold increased survival, compared with a 1.2-fold increased survival after systemic administration of BCNU. These results suggested that this short-term delivery of BCNU from PLGA wafers may be useful in the development of implantable polymeric device for malignant glioma and clinical trials.