Preparation Of PLA Sustained Release Particles And Wafers And Their Application On The Field Of Ophthalmic And Glioma Therapy

Poly(D,L-lactide)(PLA) have emerged as a class of biodegradable polymers used and studied widely for pharmaceutical use due to its biocompatibility and biodegradability. In this dissertation, drug loaded PLA particles and wafers were prepared respectively, and their applications in ophthalmic and glioma therapy were studied.To inhibit the immunologic rejection after corneal transplantation, cyclosporine-loaded or Rapamycin-loaded PLA/PEG wafers were prepared, respectively. Addition of PEG to PLA wafer can adjust the drug release ratio, and the drug release follows zero degree release dynamic. The results of animal experiment showed that the RAPA-PLA/PEG wafers had the same treatment effect as CyA-PLA/PEG ones, same results can also obtained by combining treatment of RAPA with CyA under lower dose condition.For the same purpose, CyA-loaded PLA particles were prepared by solvent evaporation process using chitosan-g-cholestorol amphiphilic polymer as surfactant. TEM and DLS measurement showed that the particles were of regular round shape with smooth surface and narrow size distribution. XPS measurement demonstrated the existence of Cs-Chol on the surface of PLA particles. Encapsulation ratio, encapsulation yield and in vitro release of particles were measured by UV method. Results indicated that encapsulation ratio and encapsulation yield increased with CyA and Cs-Chol concentration. Particles with small particle size and large drug content released fast. The immunologic rejection of the drug-loaded particles was confirmed by animal experiment.For brain glioma therapy, BCNU-loaded nanoparticles were prepared using Pluronic F68 as surfactant. The influences of pH of F68 solution and concentration of F68 on the particle size, encapsulation ratio and encapsulation yield of the BCNU-loaded nanoparticles were studied by adjusting the micellar behavior of F68 through changing pH of F68 solution and concentration of F68. Drug release in vitro indicated that BCNU loaded PLA nanoparticles were characterized by controlled release effect which was also demonstrated by the inhibit of brain glioma in vivo.