Study On The Preparation And Performance Of Multifunctional Pla Microcapsules

Polymeric microcapsules have attracted increasing attention in recent years due to their wide application prospects in biomedical fields, such as drug delivery systems, blood substitutes, ultrasound contrast agents and so forth. On this basis, incorporation of different inorganic nanoparticles into polymeric microcapsules can provide the desired acoustic, magnetic, optical, thermal or other property to the microcapsules. Polymeric microcapsules incorporating superparamagnetic Fe₃O₄ nanoparticles in its shell or cavity can serve as a dual functional contrast agents both for magnetic resonance imaging (MRI) and ultrasound imaging. In this dissertation, poly(lactic acid) (PLA) was chosen to be the shell material for FDA's approval of clinical use, and appropriate method was adopted to fabricate PLA microcapsules with controllable size, shell structures, composite structures and magnetite loading. Sound attenuation spectra covering the medical ultrasound frequency were used to investigate the sound attenuation and resonance frequency of the microcapsules.Firstly, poly(lactic acid) microcapsules with controllable average size were fabricated by the improved double emulsion– solvent evaporation technique. Considering the importance of hollow structure to the function of microcarrier, we introduced the concept of"hollow ratio"and"hollow degree"to semi-quantitatively evaluate the hollow structure of the microcapsules. It was demonstrated that the W1/O volume ratio in the first emulsification process was of vital significance to the hollow ratio, and a too high or too low W1/O volume ratio was not favorable to the output of hollow microcapsules. Moreover, a suitable concentration of emulsifier in the outer aqueous phase can guarantee a high hollow ratio. It was also found that the size of inner aqueous droplets has great effect on the size of the microcapsules, and lower energy input of the second emulsification process could obtain bigger microcapsules with multicavities. With a good comprehension of the mechanism on structure formation and size variation, we successfully fabricated poly(lactic acid) microcapsules with high hollow ratio, single cavity and adjustable average size of 12μm, 10μm, 8μm, 6μm, 5μm and 4μm. On the basis of the work mentioned above, oil-soluble Fe₃O₄ nanoparticles synthesized by thermal decomposition were compounded with poly(lactic acid) macromolecular by double emulsion– solvent evaporation method to obtain magnetic poly(lactic acid) microcapsules with Fe₃O₄ nanopartilces composited in the shell. When the magnetite loading was 13 wt.%, the corresponding saturation magnetization was 4.6 emu/g. Through carefully adjusting the parameters in the second emulsification, the regularity in the transformation of shell structures was firstly explored. With the increase of the energy or the time of the second emulsification, the composite microcapsules transformed from honeycomb gradually to multicavity, concentric, eccentric, bowl, crater and finally to solid structures, accompanied by the decrease of average size. The variation of shell structure caused the change of surface morphology. The concentric microcapsules had smooth and tight surface, which had no difference from that of solid microspheres. While eccentric and multicavity microcapsules had holes on the surface which led to the inner cavities.In order to obtain the magnetic poly(lactic acid) microcapsules with Fe₃O₄ nanoparticles composited in the cavity, a novel interfacial coprecipitation joint double emulsification method was designed and verified. In this method, iron salts aqueous solution served as the inner aqueous phase, di-n-propylamine was dissolved in PLA/dichloromethane solution and served as the oil phase. The interfacial coprecipitation which generated water-soluble Fe₃O₄ nanoparticles performed at the water in oil (W1/O) interface of double emulsion. After Fe₃O₄ nanoparticles generated at the water in oil (W1/O) interface, they would transfer into the inner aqueous phase due to their hydrophilicity. The inner aqueous phase was the precursor of cavities, so the Fe₃O₄ nanoparticles remained in the cavities after the inner aqueous phase was sublimated by freeze drier, and poly(lactic acid) microcapsules with magnetic cavity were obtained finally. This approach realized the simultaneous synthesis of magnetic nanoparticles and polymeric microcapsules and greatly simplified the fabrication process of magnetic composite microcapsules. It was demonstrated that increasing the input of iron salts and prolonging the time of ultrasonic vibration could obtain magnetic poly(lactic acid) microcapsules with a magnetite loading of 38 wt.% and a relevant saturation magnetization of 22 emu/g. Through investigating the mechanism of synthesis, we considered that the ultrasonic vibration accelerated the performance of interfacial coprecipitation and caused the saturation magnetization of the generated Fe₃O₄ nanoparticles to achieve 78 emu/g, and finally enhanced the magnetic properties of composite microcapsules.Sound attenuation spectra covering the medical ultrasound frequency (0-10 MHz) were used to investigate the influence of size, shell structure, composite structure and magnetite loading on the sound attenuation and resonance frequency of the poly(lactic acid) microcapsules. With the average size increased, the resonance frequency improved accordingly, but the sound attenuation did not change obviously. The resonance frequency and the sound attenuation in the entire spectrum of concentric microcapsules were higher than that of crater and multicavity. Microcapsules with multicavities had the lowest resonance frequency due to their porous and loose shell structures. With the magnetite loading in shell improved from 0 wt.% to 13 wt.%, the resonance frequency and sound attenuation improved gradually. When the magnetite loading in cavity increased from 12 wt.% to 38 wt.%, the resonance frequency had no variation, but the sound attenuation in the entire spectrum decreased. The different influence of magnetite loading in shell and magnetite loading in cavity reflected the influence of composite structures on the acoustical properties of microcapsules. In vitro ultrasonography demonstrated that poly(lactic acid) microcapsules with 13 wt.% magnetite loading in shell had higher video intensity than pure poly(lactic acid) microcapsules, which was consistent with the measured results of their sound attenuation.