發炎反應，是人體內重要的免疫、警示。正常的發炎反應，是避免外來入侵物堆積、傷害身體的重要防線。但是，過度或不正常的發炎反應，往往造成體內組織無法回復的傷害，其抑制與調控，便顯得非常重要。硫辛酸(Alpha lipoic acid, ALA)，即是當今十分重要的親水性抗發炎藥物，也是體內細胞代謝作用中非常重要的補體。只是，親水性藥物在體內往往容易被組織液大量稀釋，造成投藥區域藥物濃度損失，往往需要投入比預期更大量的藥物，才能達到藥效。因此，本研究希望透過藥物載體粒子的包覆，達到ALA於投藥環境中穩定釋出的效果。澳洲茶樹精油(Tea tree oil, TTO)，為一複方油性藥物，內含數種可能據有抗發炎效果的物質，但由於極差的親水性，導致很難用於藥物試驗。因此，本研究希望透過藥物載體粒子的包覆，使TTO可以均勻地分散於PBS中，進而能直接用於藥物試驗。幾丁聚醣(Chitosan, CS)，為現今相當熱門的天然高分子藥物包覆材料，其黏膜組織沾黏性及生物相容性廣為人知，非常適合用於本研究中的藥物包覆材料。電噴霧技術(Electrospray, ES)為一創新次微米藥物載體粒子備製技術，近年來廣泛應用於藥物載體粒子領域研究中。ES技術使用的設備簡單，且只需單一步驟即可完成粒子備製，並且可於常溫常壓下進行，非常便利、實用。本研究中利用ES技術成功備製出ALA-PEO-CS、TTO-PVP-CS兩種次微米級抗發炎藥物載體粒子，並進行結構特性鑑定。ALA-PEO-CS的平均粒徑為707.5 ± 66.6 nm，而TTO-PVP-CS為659.8 ± 229.0 nm，兩者在表面形態與上皆為飽和球型。體外抗發炎試驗部分，在CS次微米藥物載體粒子包覆下ALA-PEO-CS相較於單純未包覆的ALA，有較好的抗發炎效果，提升了ALA藥物近100 %的使用效率。另外，經次微米藥物載體粒子包覆後，TTO-PVP-CS成功均勻地分散於PBS中，並於體外抗發炎試驗中達到良好的效果。我們相信，ALA-PEO-CS和TTO-PVP-CS非常有淺力成為創新抗發炎藥物的優良選擇。

This study demonstrates the feasibility of using a single- capillary electrospray (ES) system to generate novel alpha-lipoic acid (ALA) encapsulated poly(ethylene oxide)-chitosan, and tea tree oil (TTO) encapsulated poly(vinylpyrrolidon)-chitosan (ALA-PEO-CS and TTO-PVP-CS) particles with monodispersed diameters. Scanning electron microscopic images (SEM) and dynamic light scattering (DLS) results indicate that the ES system can generate either a dry powder or a homogeneous water-based suspension of ALA-PEO-CS and TTO-PVP-CS particles. The SEM images revealed that both ALA-PEO-CS and TTO-PEO-CS particles have spherical shape with diameters of approximately 707 ± 66.68 nm, and 659.8 ± 229.0 nm. In addition, zeta potential studies were performed using a zetasizer instrument and showed positively electric surface potential of 57.7 ± 0.5 mV of ALA-PEO-CS , and almost neutral -4.1±0.01 mV of TTO-PVP-CS. Based on the zeta potential studies, we concluded that the excellent dispersity and stability of ALA-PEO-CS and TTO-PVP-CS suspension is attributed to the reduction in particle size and electrostatic repulsion between these submicron particles. Besides, TTO no longer suffered from its poor solubility in drug evaluation, because of the result above. Finally, we used lipopolysaccharide (LPS)-induced nitrite formation in Raw 264.7 macrophages as a model for in vitro anti-inflammation evaluation. We find that the anti-inflammatory ability of the ALA-PEO-CS particles is superior to that of free ALA solution in macrophage cells, which is attributed to the more efficiently intracellular delivery. The confocal image results proved that the uptake of ALA-PEO-CS particles by the LPS-treated Raw 264.7 macrophages is possibly initiated by the interaction with cell-surface molecules through electrostatic interactions, followed by endocytosis of the attached particles. TTO, also showed good anti-inflammatory effect in LPS test, which is attributed to all the effective components were carried in the carriers. We believe that ALA-PEO-CS and TTO-PVP-CS have great potential as novel formulation for anti-inflammatory treatment.

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