Preparation And Characterization Of Drug-loaded PLGA Microspheres Featured With Magnetocaloric Effect

Magnetic material has a wide range of applications in cell separation, immunoassays and targeted drug delivery. Magnetic PLGA microspheres have tremendous potentials in magnetic targeting drug delivery system due to its good biocompatibility and unique magnetic properties. However, the traditional methods of preparing PLGA microspheres, such as solvent evaporation, double emulsification, spray-drying, are difficult to accurately control the particle size of microspheres, which will result in a broad particle size distribution and limit its application. Compared with traditional preparation methods, the microchannel method can prepared PLGA microspheres with narrow particle size distribution and good dispersity. In addition, the microchannel method shows a good reproducibility, and better controllability.In this paper, Fe3O4 nanoparticles(Fe3O4 NPs)were papered by the solvent thermal method and pyrolysis method, respectively. The magnetic particles with uniform size were obtained by selecting the optimum preparation conditions. The stable emulsions of Fe3O4 NPs were used as the core material, and PLGA of remarkable biocompatibility was used as the wall material. Based on the micro-fluids technology, encystment performed via DCM evaporation in a microchannel. By optimizing the preparation conditions, the monodisperse magnetic microspheres of different sizes were obtained. The crystal form and size of the Fe3O4 NPs were characterized by using XRD. The ingredients of magnetic microspheres were determined by FTIR. The proportion of magnetic microspheres was evaluated by using thermal-gravimetric analysis(TGA). The magnetic performance of magnetic microspheres was determined by VSM. The morphology and structure of the magnetic microspheres were characterized by using TEM and metalloscope. Subsequently, the glucose solutions with different concentration were added to regulate the osmotic pressure of the external water phase. As a result, magnetic microspheres of different sizes were obtained. Curcumin, which has a remarkable anti-tumor efficiency, was added to the emulsion to prepared drug-loaded PLGA magnetic microspheres. The coating ratio, loading efficiency and release of curcumin in vitro of magnetic microspheres were also studied.The main results are summarized as follows:(1) Preparation of Fe3O4 nanoparticle and the stability of the W/O initial emulsionThe saturation magnetization of Fe3O4 nanoparticle papered by the solvent thermal method and pyrolysis method is 88.5734 emu·g-1 and 82.4065 emu·g-1 respectively. The crystallinity and hydrophilia of the sample prepared by the solvent thermal method are better than that of pyrolysis method. The mean particle size of Fe3O4 nanoparticle depends on the concentration of precursor in the solvent thermal method. When concentration of Fe3+ was constant, the mean particle size of Fe3O4 nanoparticles decreased with increasing the volume ratio of ethylenediamine to glycol. Particle size and morphology of Fe3O4 nanoparticles can be controlled by reaction temperature or holding time.At room temperature, Fe3O4 nanoparticles as core of capsules, PLGA(characteristic viscosity: 1.50 dL/g) as oil phase, the optimal parameter of emulsifying was 8000 r/min in 3min. The W/O initial emulsion can remain stable for 24 h, which could be used in the microchannel for preparation of magnetic PLGA microspheres.,(2) Preparation of magnetic PLGA microspheres with microchannel device and the controllable particle size.Monodisperse magnetic PLGA microspheres can be successfully prepared in the 5 m long microchannel with 500 μm inner diameter, when the velocity ratio of external aqueous phase with 1wt.% PVA to W/O initial emulsion was 120:1. The Fe3O4 content in the magnetic PLGA microspheres was 6.4% and the encapsulation efficiency was calculated to be 90.1%. The saturation magnetization of magnetic PLGA microspheres is up to 3.2846 emu·g-1, as well as almost zero remnant magnetization, indicating the good superparamagnetic property. The maximum magnetic entropy of the PLGA microspheres was 325 K. Moreover, Mean particle size of the microspheres was confirmed to be controllable from 16 μm to 207 μm with glucose concentrations in external aqueous phase varying from 0 wt. % to 20 wt. %. The higher glucose concentration brings about the smaller mean particle size.(3) Drug release performance of the magnetic PLGA microspheresCurcumin, a drug with inhibitory effect on tumor cells was used to exemplify the releasing properties of the magnetic PLGA microspheres. Monodisperse magnetic curcumin-loaded PLGA microspheres could be successfully obtained in the microchannel when a curcumin solution in 1, 2-propanediol solution was mixed to form internal aqueous phase. The drug loading ratio and the encapsulation efficiency of magnetic PLGA microspheres was 3.2% and 77.9% respectively. Release ratio was up to 15.0% within 1 h in a phosphate buffered solution containing 0.5% sodium lauryl sulfate. A releasing ratio of 72.4% curcumin from the magnetic PLGA microspheres was achieved within 120 h. After 240 h, the release ratio topped off at 84.8%. Therefore, the magnetic curcumin-loaded PLGA microspheres took on a reasonably slow release effect, which would be applicable to tumor magnetic targeted drug therapy.