此論文中以同軸電噴射(coaxial electrospraying)製造幾丁聚醣(chitosan)與聚乳酸(polylactide, PLA)之核殼型(coreshell)奈米粒子。第一部分探討不同的操作條件包含：流率、電壓、操作距離、溶液濃度等對粒子製備的影響，進而找出製造具有最小及最均勻粒徑之奈米粒子的最佳化條件。結果顯示製備幾丁聚醣奈米粒子最佳化條件為：流率0.5 ml/h 、電壓22 kV 、操作距離12 cm 、幾丁聚醣濃度5 g/L 。而製備核殼型奈米粒子的最佳化條件與上述大致相同，添加0.5 % PLA後，改變操作距離縮短成10 cm，此改變是由於核殼型需要更高的電壓梯度去製備球狀的奈米粒子。
接著我們藉由培養UMR-106及PC-12細胞，分析奈米粒子之生物相容性及進入細胞的能力。結果顯示，細胞活性隨著奈米粒子濃度上升與培養時間延長而減少。在低粒子濃度的情形下，幾丁聚醣奈米粒子和核殼型顆立皆有非常高的生物相容性。此外，奈米粒子的存在並不會影響到PC-12細胞的分化。
為了測試奈米粒子在藥物傳遞上的潛能，兩種不同型態的奈米粒子被載入牛血清白蛋白(BSA)並觀察釋放動力模式。釋放曲線分為兩個階段，在第一階段中，BSA的累積釋放濃度快速地隨時間上升，此階段主要是釋出在顆粒表層的蛋白質。在第二階段中，BSA累積釋放濃度上升的速率明顯地下降，此階段主要是釋出包覆於顆粒內部的蛋白質。結果顯示PLA表層可以降低第一階段中的突釋(burst release)行為，能得到緩釋型的較長效釋放曲線。此外，藉由物理吸附及臭氧活化的化學修飾，RGD成功地被固定在幾丁聚醣奈米粒子和核殼型奈米粒上，RGD固定後之奈米粒子型態並無顯著改變。
藉由體外(in vitro)腦血管障壁(blood brain barrier, BBB)模式的建立，我們得以估算奈米粒子在BBB中的滲透率。結果指出相較於幾丁聚醣奈米粒子，核殼式粒子顯示出較高的滲透率，這是因為PLA的高疏水性增加奈米粒子對細胞膜與緊密連接(tight junction)層的穿透。本研究設計了核殼雙層具有相異性質的核殼式奈米粒子，並將其電噴設製程加以最佳化，最後證實電噴製備之核殼型奈米粒子可當作藥物傳遞之載體穿過BBB。

In this study, chitosan and chitosan-polylactide (PLA) coreshell nanoparticles were fabricated by coaxial electrospraying setup. In the first part, operation conditions for fabrication of smallest and uniform particles were investigated. The flow rate, applied voltage, working distance and polymer concentration were optimized in this research. Meanwhile, the obtained nanoparticles were characterized for their particle size, zeta potential and chemical composition. For chitosan nanoparticles, the optimized conditions were the flow rate of 0.5 ml/h, the applied voltage of 22 kV, the working distance of 12 cm and the chitosan concentration of 5 g/L. The optimized conditions for preparation of coreshell nanoparticles were basically the same, except for the PLA concentration of 0.5 % and the working distance of 10 cm which was longer than that used for chitosan electrospraying because coreshell needed higher voltage gradient in order to produce spherical nanoparticles. The diameters for chitosan and coreshell nanoparticles were 326 and 344 nm, respectively.
The analysis of biocompatibility and cellular uptake of nanoparticles were conducted by culturing UMR and PC 12. UMR is an osteogenic cell line and PC12 is renal medulla-derived nerve cells. The results from both of UMR and PC12 indicate that cell viability decreased by increasing nanoparticle concentration and incubation time. With low particle concentration, chitosan and coreshell nanoparticles showed great biocompatibility. The presence of nanoparticles would not affect PC 12 cells differentiation in particular.
To evaluate nanoparticles potential in drug delivery, both nanoparticles were loaded with model protein, BSA, and the releasing kinetics were observed. The sizes of chitosan and coreshell nanoparticles slightly increased due to BSA loading. The release profiles verify the two-stage releasing where a long-term delivery would be approached in the second stage. Releasing from chitosan nanoparticles was faster that from coreshell ones. More important, by modifying PLA concentration, releasing profile from coreshell nanoparticles can be tailored.
RGD was successfully immobilized on chitosan and coreshell nanoparticles by physical adsorption and chemical modification induced with ozone activation. The successful immobilization of RGD was identified from EDS analysis, and the morphology of both nanoparticles was not changed significantly after RGD immobilization.
Mouse brain endothelial cells were cultured on polycarbonate (PC) membrane to establish in vitro blood brain barrier (BBB) model in this research, so the permeation of nanoparticles in BBB was able to be evaluated. Coreshell nanoparticles demonstrated higher permeability compared to the chitosan nanoparticles. This was due to the hydrophobicity of PLA that helped enhance penetration through the barrier. In summary, this research optimized the electrospraying process for the fabrication of coreshell nanoparticles and demonstrated the potential of electrosprayed coreshell nanoparticles as a drug carrier to penetrate BBB.

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