Fabrication Of PLLA Biomicrospheres Via Phase Inversion Emulsion And Their Drug Delivery Behavior

The drug loaded microspheres are a new kind of pharmaceutican formulations,which ca n achieve long-term sustained release by the regulation and controlling the release rate of dru gs.In this work,a facile,scalable technique was developed to produce biodegradable porous microspheres by combining an oil-in-oil(O/O)surfactant-free phase inversion emulsion tech nique with thermally induced phase separation(TIPS)method.The porous microspheres wer e used as drug carriers to research there drug carrying ability.This paper is divided into the following two parts:Part ?:In this work,a facile,scalable technique was developed to produce biodegradable porous microspheres by combining an oil-in-oil(O/O)surfactant-free phase inversion emulsion technique with thermally induced phase separation(TIPS)method.The effects of PLLA concentration,stirring speed,macromolecule weight and organic solvents on the size and microstructure of microspheres were investigated by scanning electron microscopy(SEM)and analysis software(Nano Measurer 1.2 software).The results revealed a highly porous structured microsphere with controllable sizes and morphologies by tuning the synthesis conditions.When we choose THF as solvent,the microsphere has a fiber-like structure with a diameter ranged from 50 to 500 nm.When using Diox as solvent,the microsphere consists of numerous nanoscale coral textures on the outer surface and many larger micro-holes with diameters of 1-2?m in the interior.For the mixed solvents system,the morphology demonstrates a transition state of combining PLLA bundled nano-fibers and nanoscale coral structure.The in vitro cytotoxicity assay demonstrated that PLLA microspheres are biocompatible.The drug-loaded experiment shows that the drug loading of D-PLLA and T-PLLA microspheres were 7.2% and 10.6% separately.The in vitro sustained release performance of the two different structures microspheres were good and the cumulative release amount for 8h were 41.2% and 75.3% separately which shows the microspheres were good drug carrier.By comparison,the drug loading of T-PLLA microspheres was higher and the in vitro sustained release existence sudden release phenomenon.Part ?: The polylactic acid / hydroxyapatite(PLLA / HA)composite microspheres were prepared by soaking the PLLA microspheres prepared above in 1.5 times simulated body fluid(SBF)with different time.The morphology,the coverage degree and crystal size of HA deposited layers were characterized by SEM.Transmission electron microscopy(TEM)results revealed a lamellar structure of HA crystals.TEM-EDS measurement showed that the Ca / P atomic ratio was 1.4 which is close to the theoretical ratio of HA.The spacing of crystal lattice planes of(110)and(002)and the characteristic diffraction peak of(002),(211),(300)and(222)were detected by high-resolution TEM and X-ray diffraction(XRD),respectively.FTIR spectra verified that the PLLA / HA composite microspheres have the characteristic peaks of both PLLA and HA.The drug-loaded experiment shows that the drug loading of D-PLLA/HA microspheres is 6.1% and the in vitro sustained cumulative release amount for 24 h were 89.7% which shows the microspheres were good drug carrier.The drug loading of T-PLLA/HA microspheres is 8.1% and the cumulative release amount for 24 h were93.9%.However,the in vitro sustained release has a burst release phenomenon.