Tae Kun An

BCNU-loaded poly(D, L-lactide-co-glycolide) wafer and antitumor activity against XF-498 human CNS tumor cells in vitro.

Implantable polymeric device that can release chemotherapeutic agent directly into central nervous system (CNS) has had an impact on malignant glioma therapy. The purpose of our study was to develop an implantable polymeric device, which can release intact 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for long-term period over 1 month, and to evaluate its cytotoxicity against XF 498 human CNS tumor cells in vitro. BCNU was incorporated into biodegradable poly(D,L-lactide-co-glycolide) (PLGA), by using spray-drying method. BCNU-loaded PLGA microparticles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction, and differential scanning calorimetry. SEM observation of the microparticles showed that the microparticles were spherical, i.e. microspheres. Homogeneous distribution of BCNU in PLGA microsphere was confirmed by significant reduction of crystallinity of BCNU. Microspheres were fabricated into wafers with flat and smooth surface by direct compression method. In vitro release of BCNU in pH 7.4 phosphate buffered saline was prolonged up to 8 weeks after short initial burst period. Antitumor activity of BCNU-loaded PLGA wafer against XF 498 human CNS tumor cells continued over 1 month and, PLGA only did not affect the growth of the cells. Meanwhile, the cytotoxic activity of BCNU powder disappeared within 12 h. These results strongly suggest that the BCNU/PLGA formulations increase release period of carmustine in vivo and also be useful in the development of implantable polymeric device for malignant glioma.

Preparation of 5-fluorouracil-loaded poly(L-lactide-co-glycolide) wafer and evaluation ofin vitro release behavior

The controlled delivery of anticancer agents using biodegradable polymeric implant has been developed to solve the problem of penetration of blood brain barrier and severe systemic toxicity. This study was performed to prepare 5-FU-loaded poly(L-lactide-co-glycolide) (PLGA) wafer fabricated microparticles prepared by two different method and to evaluate their release profile for the application of the treatment of brain tumor. 5-FU-loaded PLGA microparticles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (XRD), and differential scanning calorimetry (DSC). SEM observation of the 5-FU-loaded PLGA microparticles prepared by rotary solvent evaporation method showed that 5-FU was almost surrounded by PLGA and significant reduction of crystallinity of 5-FU was confirmed by XRD. In case of release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by mechanical mixing, the release profile of 5-FU followed near first order release kinetics. In contrast to the above result, release profile of 5-FU from 5-FU-loaded PLGA wafer fabricated microparticles prepared by rotary solvent evaporation method followed near zero order release kinetics. These results indicate that preparation method of the 5-FU-loaded PLGA microparticles to fabricate into wafers was contributed to drug release profile.