Preparation And Characterization Of Environment-Responsive Nanoparticles And Microspheres As Drug Delivery System

With the rapid growth in the field of biotechnology and biomaterials, the microspheres and nanoparticles technology provided a new ideas and methods for drug administration system. In this work, two kinds of microspheres were respectively fabricated by using natural and synthesized polymer materials; two kinds of inorganic/organic hybrid composites based on mesporous silica nanoparticles (MSNs) and environmental-responsive polyelectrolyte multilayers have been developed via the layer-by-layer (LbL) self-assembly technique. These hybrid composites could be potentially applicable as carriers with the function of drug releasing in sequence in bone tissue engineering applications. The thesis includes four parts:Part Ⅰ:Biodegradable gelatin was used as a carrier, and the gelation microspheres containing fluorescein isothiocyanate (FITC) were fabricated by the method of emulsifying and cross-linking technique. The scanning electron microscopy (SEM), fluorescence microscopy and UV-Spectroscopy were used to characterize the morphology, micoparticles size distribution, average particle diameter and drug loading of gelation microspheres. The results showed that the gelation microparticles were in good shape with smooth surface and a relative homogeneous size. The average particle size and the drug loading value were35.59±14.14μm and0.08±0.02μg/mg, respectively. Therefore, the preparation procedure of gelation microspheres established is stable and practical, and the obtained microspheres showed good characteristics.Part Ⅱ:Biodegradable poly (lactic-co-glycolic acid)(PLGA) was used as a carrier, and the PLGA microspheres containing fluorescein isothiocyanate (FITC) were fabricated by using a double emulsion method. The SEM, fluorescence microscopy, transmission electron microscopy (TEM), laser diffraction size analyzer and UV-Spectroscopy were then applied to characterize the morphology, structure, particle size distribution and mean diameter of PLGA microspheres. The results indicated that the microspheres exhibited well-controlled core-shell structure, uniform size distribution, high drug loading and drug encapsulation efficiency, which make it a potential candidate as growth factors loaded sustained-release carriers in bone tissue engineering applications.Part Ⅲ:Two types of environmental-responsive nanoparticles-carriers for "intelligent" release of model drug molecules including doxorubicin hydrochloride (DOX) and fluorescein isothiocyanate (F1TC). One system was based on alternatively coating sodium alginate (ALG) and chitosan (CHI) onto amine-functionalized mesoporous silica nanoparticles (MSNs) to load and release the positively charged drug doxorubin (DOX). The other system was synthesized by alternatively loading poly(allylamine hydrochloride) and sodium poly(stryrene sulfonate) onto MSNs for loading and releasing of the negatively charged FITC. Controlled release of the drug molecules from these delivery systems was achieved by changing the pH value of the release medium. The in vitro release studies revealed that the drugs including FITC and DOX release, respectively, from ALG/CHI-NH2-MSNs and PAH/PSS-MSNs were pH-responsive. Therefore, the surface-functionalized MSNs developed here provide efficient way to control the drug release by pH stimuli, making them suitable for a pH-responsive targeted drug delivery and cancer therapy.Part Ⅳ:Mesoporous silica nanoparticles (MSNs) with controllable size and shape were synthesized under a neutral condition. The effects of temperature, surface active agent, additive agent and relative addition rate of silica source on particle size and the dispersivity of MSNs were study. The result showed that MSNs became bigger and more uniform in size with the increase of the temperature. The use of Brij-58resulted in the improved dispersity and regularity of spherical shape. Glycerol as additive effectively improved the monodispersivity of MSNs. The reduction of the addition rate on silica source further contributed to the uniformity and bigersize of result MSNs. In summary, the particle size and shape of MSNs can be tuned by using the optimal synthesis conditions for specific biomedical applications. In addition, the neutral pH synthesis can broaden the applications of mesoporous material in biomedical areas.