Temozolomide/PLGA microparticles and antitumor activity against Glioma C6 cancer cells in vitro

The purpose of the present study was to develop implantable poly(d,l-lactide-co-glycolide) (PLGA) microparticles for continuous delivery of intact 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]-as-tetrazine-8-carboxamide (temozolomide, TM) for about a 1-month period and to evaluate its cytotoxicity against Glioma C6 cancer cells. The emulsifying-solvent evaporation process has been used to form TM-loaded PLGA microparticles. The influences of several preparation parameters, such as initial drug loading, polymer concentration, and stirring rate were investigated. Scanning electron microscopy (SEM) showed that such microparticles had a smooth surface and a spherical geometry, i.e. microspheres. The differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD) results indicated that TM trapped in the microparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The release profiles of TM from microparticles resulted in biphasic patterns. After an initial burst, a continuous drug release was observed for up to 1 month. Finally, a cytotoxicity test was performed using Glioma C6 cancer cells to investigate the cytotoxicity of TM delivered from PLGA microparticles. It has been found that the cytotoxicity of TM to Glioma C6 cancer cells is enhanced when TM is delivered from PLGA polymeric carrier and, PLGA only did not affect the growth of the cells. Meanwhile, the cytotoxic activity of TM powder disappeared within 12 h.