Preparation Modification And Application Of Biodegradable Microspheres

Porous poly (D,L-lactide-co-glycolide)(PLGA) microspheres were prepared by emulsion solvent evaporation method. Preparation parameters were adjusted to obtain microspheres with different morphology and tested their BSA release behavior. The surface of PLGA microspheres was decorated with polystyeren (PS) nanoparticles and polycaprolactone (PCL) nanoparticles through a simple and efficient approach, obtaining PLGA/PS and PLGA/PCL micron-nano structured composite microspheres. The influences of immersion time, nanoparticles’concentration and surface treatment on the composite microspheres were studied. These composite microspheres offered a multi-structured topography for cell growth.The influences of inner aqueous phase, organic solvent, PLGA concentration on the morphology of microspheres were studied. The results showed that addition of porogen or surfactants to inner aqueous phase, types of organic solvents and polymer concentration had a great effect on microsphere morphology. When dichloromethane was adopted as organic solvent, microspheres of uniform porous structure were produced and the morphology of microspheres didn’t change with the variation of PLGA concentration. When ethyl acetate served as organic solvent, two different morphologies were obtained. One was hollow microspheres with thin porous shell under a lower PLGA concentration, the other was erythrocyte-like microspheres under a higher PLGA concentration. Three types of microspheres including uniform porous, hollow core with thin porous shell (denoted by hollow in brief) and solid structures were finally selected for in vitro drug release test. BSA was chosen as model drug and encapsulated within the microspheres. The BSA encapsulation efficiency of uniform porous, hollow and solid microspheres was respectively90.4%,79.8%and0. And the ultimate accumulative release was respectively74.5%,58.9%and0. The release rate of uniform porous microspheres was much slower than that of hollow microspheres. The experiment results indicated that microspheres with different porous structure showed very different drug release behavior.In the experiment of PLGA/PS micron-nano structured composite microspheres, the influence of surface modification method, nanoparticles’ concentration and immersion time on the distribution of nanoparticles on the surface of PLGA microspheres were studied. There were three effective surface modification method:poly(1-lysine)(PLL) absorbed PLGA microspheres-sulfonated PS nanoparticles, surface of PLGA microspheres were homogeneously distributed a large number of nanoparticles; Aminolyzed PLGA microspheres-sulfunated PS nanoparticles, surface of PLGA microspheres were distributed many nanoparticles; unmodified PLGA microspheres-unmodified PS nanoparticles, a great many nanoparticles distributed nonuniformly on the surface of PLGA microspheres. The reasonable experimental parameters were:2-6mg/ml of nanoparticles concentration;12-24hours of immersion time, nanoparticles increased with increase of immersion time, but the immersion time must be within24hours because the amount of sulfonated PS nanoparticles would sharply decrease resulting from hydrolysis of PLGA promoted by sulfonated PS.In the experiment of PLGA/PCL micron-nano structured composite microspheres, the influence of nanoparticles’concentration and immersion time on the distribution of nanoparticles on the surface of PLGA microspheres were studied, and the mechanism of combination between PLGA microspheres and PCL nanoparticles were explored. The suitable experimental parameters were: nanoparticles’concentration≥2mg/ml, immersion time≥12hours. The amount of nanoparticles increased with increase of immersion time. There existed an acting force between PLGA microspheres and PCL nonaparticles. PCL nanoparticles and PLGA microspheres were together more than physical spatially. To further identify the formation of chemical bonds between PLGA microspheres and PCL nanoparticles, experiments with addition of catalyst were conducted. This catalyst can promote the reaction of carboxyl and amine. According to the SEM photographs, addition of catalyst greatly increased the nanoparticles on the microspheres. But it remained unclear that chemical bonds formed between PLGA microspheres and PCL nanoparticles.