Summary: | 碩士 === 國立臺灣科技大學 === 化學工程系 === 96 === The purpose of this work was to prepare the biodegradable PLGA nano-particle encapsulating the drug which can promote the bone regeneration. Firstly, we have investigated the effect of emulsion times and polymer molecular weight on the size of nano-particles and encapsulation efficiency. After finding optimal conditions, three different drugs for bone regeneration were encapsulated, including BSA (Bovine Serum Albumin), Lovastatin and Alendronate. The encapsulation efficiency, releasing profile and cell responses were then investigated. The isoelectric point (pI) of BSA is similar to Fibroblast Growth Factor-1(FGF-1), so BSA was used to simulate the situation for growth factor encapsulation.
The size of the particles could be controlled by changing the emulsion time in preparing process. From the TEM (Transmission Electron Microscope) and SEM (Scanning Electron Microscope) pictures, it showed that the particles were uniform and smooth spheres. The particles have been also proved to be biocompatible by the MTT assay.
With optimized conditions, the encapsulation efficiency of PLGA nano-particles was 60.65% for BSA, 78.45% for lovastatin and 77.39% for Alendronate. All the particle size would be around 200 nm in diameter, which is suitable for the drug delivery system. In order to retard the decrease in pH due to the PLGA degradation, CaCO3 and NaHCO3 were used as neutralizer agent in this study. The experimental results suggested that the self-catalyzed degradation would be suppressed by the addition of neutralizer agents; that is to say, the long-term release would be thus reached.
The release of BSA from nano-particles is stable for 2 months in a controlled buffer system. According to the observation of fluorescent BSA in the in vitro system, the nano-particles prepared in this research would be untaken into osteoblastic-like cells (UMR-106) before 6 hours. The Lovastatin encapsulated in PLGA particles would be released in 7days, which would effectively promote the expression of ALPase.On the other hand, an acute burst release was observed for the particles with Alendronate. It is possibly due to that Alendronate is hydrophilic and with small molecular weight, resulting an easy diffusion from particles.
This research has demonstrated the particles prepared by emulsion method were uniform, biocompatible and also with high encapsulation efficiency for BSA, Lovastatin and Alendronate. It could be applicative for bone regeneration field.
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