EFFICIENT GAMMA-IRRADIATED STERILIZED BIODEGRADABLE SPRAY DRIED METHOTREXATE LOADED SUBMICROPARTICLES FOR PARENTERAL OR PULMONAR APPLICATION
Methotrexate, PLGA, Spray drying, Gamma-irradiation, Pulmonary and Parenteral Submicroparticles.
Methotrexate-loaded submicroparticles using poly-(D,L-lactide-co-glycolide) polymer (PLGA) were prepared by a spray-drying method and the effects of gamma-irradiation in the microparticles were investigated. Microparticles were irradiated with 60Co at 15, 25 and 30 kGy to investigate both the effect of drug and charge into microspheres. The physicochemical characterization included drug assay by HPLC, Scanning Electron Microscopy (SEM), particle size, Infrared Spectrophotometry (FTIR), X-ray analysis and Electron Paramagnetic Resonance (EPR). In vitro drug release studies of microparticles were performed in phosphate buffer pH 7.4 (0.05M) medium thermostatized 37°C ± 0.2°C and subjected to different kinetics release models. The assay of cell activity was realized using Vero and Siha lines cells. Systems no-irradiated and irradiated shows smooth surface and spherical shape with average size about 5 to 6 µm. The drug-loading efficiency remained greater than 87.23% and FTIR spectra did not shown relevant differences. The EPR signal identified radical formation in proportion to the amount of drug added in the microparticles. X -ray diffraction analysis shown that MTX was homogeneously dispersed into polymeric matrix, with a prevalent amorphous state. The in vitro release studies confirmed the sustained release for MTX-loaded PLGA microparticles and showed no significant change after sterilization. The involved drug release mechanism was mathematically adjusted by Korsmeyer-Peppas kinetic model. The microparticles appeared to have better effects for cancer cells than methotrexate and the systems showed similar equivalent biological activity after irradiation. Gamma irradiation showed to be an efficiency and safe method to provide the terminal sterilization of PLGA microparticles for methotrexate delivery system