Preparetion Of Paclitaxel-Loaded PLA, PLGA And PELA Microspheres By Premix Membrane Emulsification

Recently, many researchs focus on preparing microspheres as insoluable drug carrier because microsoheres own some advantages of improving solubility and adsorption of insoluable drug and targetable delivery. In order to overcome the problem that the size distribution of microsphere is broad with conventional methods, uniform-sized paclitaxel-loaded PLA, PLGA, PELA microspheres were prepared by premix membrane emulsification technique. In this study, surface morphology, drug distribution, drug loading efficency, encapsulation efficiency and drug release profiles were studied.The dissertation is divided into three parts. The first part focus on using premix membrane emulsification to prepare uniform-sized PLA microspheres with the index polydispersity of 0.005. The size distribution of PLA microspheres was from 900 to 1000 nm. It suggested that premix membrane emulsification has great potential on preparing uniform-sized microspheres compared with homogenization and ultrosonification emulsification. Based on this, uniform-sized PLGA and PELA microsperes were prepared. The mophology characterization suggested PLA and PLGA microsperes had smooth surface, while the surface of PELA microspheres was folded and jagged with some pore channels.In the second part paclitaxel-loaded PLA, PLGA and PELA microspheres are prepared and compared by premix membrane emulsification. The loading efficency of paclitaxel-loaded PLA, PLGA and PELA microspheres were 3.89%,4.93% and 3.18, and corresponding encapsulation efficency were 63.2%,71.6% and 51.3%, respectively. Paclitaxel exsited in PLA microspheres as fine particles. While in PLGA microspheres, paclitaxel precipited in situ and aggreated as spot adjuncts and in PELA microspheres bigger spot adjuncts were obsevered. The profile release of paclitaxel-loaded PLA, PLGA and PELA microspheres in vitro for 60 days were 83.87%,50.25% and 41.27%.The third part focused on structure regulation. Porous PLA microspheres were prepared with NH4CO3 as pore-forming agent in internal water phase. The effects of NH4CO3 concentation, ultrosonification power, time and emulsifier were studied in this part.The results suggested that premix membrane emulsification has great potenial on preparing uniform-sized microspheres comparing with conventional homogenization and ultrosonification technique. For PLA, PLGA and PELA microspheres, insoluable drug distributions were different because of the hydrophilicity of materials, furthermore, drug loading efficency, encapsulation efficency and the release profile in vitro were different. Only PLGA with suitable hydrophilicity had relative higher drug encapsulation efficency and faster ralease rate. It supposed to be chosen as suitable insoluable drug carrier.