Synthesis And Properties Of Polyvinyl Alcohol Microspheres

In resent years, microspheres have been widely used as injectable bone repair materials and drug carriers. Among the different types of microspheres, polyvinyl alcohol(PVA) materials have attracted much attention of the world due to their non-toxicity, good biocompatibility and biodegradability. However, researches on PVA currently focus on the form of hydrogels, which limits the application of this material in the biomedical field. In addition, the biological activity and mechanical properties of PVA in the application of bone tissue engineering can be effectively improved by being composited with nano hydroxyapatite(HA).In this thesis, an emulsion crosslinking method was used to prepare polyvinyl alcohol microspheres with a regularly spherical form, average particle size of 25 μm, narrow diameter distribution and good dispersity. The effects of several key experimental parameters on the preparation of PVA microspheres were discussed, and the optimal preparation parameters were determined. The influences of cross-linking agent on swelling, the drug-loading efficiency and drug release behavior of the PVA microspheres were researched. Furthermore, in-situ synthesis of the PVA/HA composite microspheres in the emulsion system was preliminary studied. The main research results can be summarized as follows:(1) The PVA microspheres were prepared by an emulsion crosslinking method, using vegetable oil as continuous phase(oil phase), aqueous PVA solution as dispersed phase(water phase), glutaraldehyde(GA) as a crosslinker, and hydrochloric acid as a catalyst. The composition, morphology and particle size distribution of the microspheres were characterized by FT-IR, SEM and particle size analyzer. The results showed that optimum PVA microspheres can be prepared when the concentration of the PVA solution was 5%, 2 g sorbitan monooleate(Span80) was used as the surfactant, the emulsification temperature was 50°C and 1 M hydrochloric acid was chosen as catalyst. Besides, a low-concentration PVA droplets appeared in the process of crosslinking which can not be cross-linked into a ball, resulting in the amorphous substance existing in microspheres.(2) The PVA microspheres with different GA agents were prepared at the optimal experiment conditions listed above, and the influence of GA agents on the swellable of microspheres was investigated. Drug-loaded PVA microspheres were prepared by soaking the microspheres in the bovine serum albumin(BSA) solution, and their drug loading and releasing behaviors were evaluated via the UV spectrophotometry. In addition, the morphology of microspheres after drug release was characterized by SEM. The results showed that PVA microspheres have a load capacity for BSA, and when the amount of GA was 0.3 ml, entrapment efficiency and drug-loading amount can be 11.08% and 33.25%, respectively. Moreover, the GA agent has a great impact on swelling and in vitro drug releasing behaviors of microspheres that both them decreased first and then increased with the increase of the amount of GA. The SEM results showed that there is no degradation of microspheres after drug releasing for 72 h.(3) The preparation method of the PVA/HA composite microspheres in the emulsion system was preliminary studied. The FT-IR, XRD, SEM and TG-DSC were used to characterize the composition, structure and morphology of the PVA/HA microspheres. The possible preparation process is: firstly, the HA was added into PVA aqueous solution in the form of Ca2+ and PO43- after being dissolve in HCl; and then the mixed solution was dispersed into the oil phase with Span80; the Na OH was last added into the system to adjust the p H to deposit HA after droplets curing. To ensure pure HA, the amount of 1 M Na OH solution was not less than 2 ml.