| Magnetic microcapsule is a new type system for targeted drug delivery in the cancer drugcarrier and tumor magnetic heat treatment recent years. It possesses both polymer properties andmagnetic responsiveness. As the polymer wall material with good biological compatibility used inthe magnetic microcapsule, poly (lactic-co-glycolic) acid (PLGA) shows better biocompatibilitythan the commonly used polymer materials, such as polyurethane (PU) and polyacrylate, and canbe eventually degraded into CO2and H2O in the human body. It is also safety and non-toxic.Therefore, it is an ideal material for drug microcapsule. However, the preparation of magneticmicrocapsule with traditional interfacial polymerization, such as solvent evaporation and spraydrying method, the size of microcapsules is inhomogenous and uncontrollable. This goes againstits clinical application as biomedicine carrier. Preparing microcapsule with microchannel reactoris simplicity to operator. And it is easy to control the distribution of microcapsule particle size tosmall and narrow, which causing good monodispersity.In this paper, hydrophilic Fe3O4nanoparticles prepared using solvothermal was used as themagnetic core material, biodegradable materials PLGA was used as wall material. The magneticmicrospheres were prepared with microchannel device combined with composite emulsionmethod. The related preparation parameters were optimized. The stability of W/O emulsion,which is the main component of composite emulsion (W/O/W) was studied in detail. The effectivecomponents of magnetic microsphere, the component ratio, the magnetism, the structure andmorphology of prepared magnetic microspheres were tested and characterized by means of FTIR,TGA, VSM (vibrating sample magnetometer), SEM and metallo-microscope. After that, themagnetic microspheres with different particle size were prepared using the microchannel device.The average particle size and size distribution of the magnetic microspheres prepared by theosmotic pressure were analyzed. The osmotic pressure brought about different concentrations ofthe outer phase, which contributed to obtain good controllable particle size and monodispersity ofPLGA magnetic microspheres. Finally, drug (aspirin)-loading PLGA magnetic microspheres wereprepared. The encapsulation, drug loading capacity and cumulative release curve in vitro were measured by using ultraviolet spectrophotometry. Moreover, the feasibility of monodispersedPLGA magnetic drug microspheres being used as magnetic targeting drug was also investigated.The main results are summarized as follows:(1) Preparation and stability of the gelatin-DCM W/O emulsionWhen preparing W/O emulsion with Fe3O4gelatin aqueous solution as water phase andPLGA in dichloromethane solution as oil phase, it is proved that the intrinsic viscosity of PLGA,temperature and pH of water phase affected the stability of W/O emulsion.Using PLGA with intrinsic viscosity of1.20dl/g as oil phase component, the duration ofW/O emulsion can be stable for more than10h. With high viscosity PLGA system andtemperature in15~20℃can conducive to forming more stable emulsion. The pH of water phasehas certain influence on the stability of emulsion from pH4to10. Alkaline condition is benefit formore stable W/O emulsion.(2) Preparation of PLGA-Fe3O4magnetic microspheres with microchannel deviceUsing microchannel device and according to composite emulsion method, the magneticmicrospheres can be prepared by adjusting the velocity ratio of W/O emulsion and outer aqueousphase. The particle size of microspheres were adjustable by the different spacing of the emulsiondroplets flowing in the microchannel. When the water phase velocity was120uL/min and oilphase flow rate was1uL/min, the magnetic microspheres exhibit good monodispersity.Monodisperse magnetic microspheres can be successfully prepared in the microchannel withFe3O4in mass concentration of0.01g/mL, PLGA in0.050g/mL, and PVA in1wt.%. The resultsshow that the content of Fe3O4magnetic microspheres was9.2wt.%, the saturation magnetizationintensity of magnetic microspheres is1.51784emu/g and the remanent magnetism is close to zero,which showing good paramagnetism. The optimum preparation parameters are: m(Fe3O4):m(PLGA)=1:10,120μL/min water phase velocity,1μL/min oil phase velocity,5m microchannellength, and330μm inner diameter of the microchannel.(3) The controllable particle size and drug release performance of the magnetic microspheresDue to the ion concentration difference between internal and external water phase by addingNaCl to the outer aqueous phase, the water in the inner phase can diffuse outward, causingrelatively smaller particle size of microspheres. When the NaCl concentrations were changed from0.2M,0.4M,0.6M, to0.8M, the resulting microspheres particle size is202μm,172μm,144μm,and123μm respectively. With the increase of NaCl concentration, microspheres particle size canreach to80μm. Furthermore, the microspheres particle size distribution is uniform, and coefficientof variation(CV) values are less than5%, showing good monodispersity. Low cost Asprin was used as the model drug to prepare PLGA-Asprin drug microspheres. Itis found that the prepared samples are in good monodispersity. It is shown that the drug loadingcapacity is13.71wt.%, and the encapsulation ratio is38.44wt.%. Drug microspheres cancontrolled release Asprin in0.9wt.%NaCl aqueous solution at37℃. The cumulative release curvein vitro showed that the drug-loaded PLGA Aspirin magnetic microspheres can release Asprinwith constant speed of different rate at three stages of0~4h,4~40h,40~60h due to the pore andPLGA swelling. As a result, magnetic microspheres, which prepared with microchannel devicecombined with composite emulsion method is expected to be used for targeted drug release. |
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