摘 要 本篇論文主要探討,以不同聚乳酸比例的PLGA高分子為基材,利用乳化溶劑揮發法,製備包覆蛋白質藥物模式的微小球。探討於乳化過程摻合磷脂質,對微小球的物理特性與體外釋放的影響。 實驗結果發現,摻合磷脂質微小球表面平滑較無孔洞分佈,且微小球的平均粒徑也有下降的趨勢。以PLGA(85:15)微小球來說,其平均粒徑從476.56um下降至330.23um。另外,摻合磷脂質微小球其蛋白質包覆效率也有明顯的降低;以PLGA(85:15)製備的微小球而言,未摻合磷脂質的微小球包覆效率為95.8%;而摻合磷脂質則降為82.27%。 至於在蛋白質體外釋放中,摻合磷脂質微小球則有明顯的延遲釋放的現象,尤其在24小時以後的釋放階段中較為明顯。以 PLGA(85:15)微小球為例,其24至288小時的釋放百分比為26.91%;而摻合磷脂質的微小球則降為15.34%。產生這項結果的原因,我們從酒精實驗中推論出可能與附著在微小球表面的磷脂質有關;另外,也有可能跟蛋白質於微小球分佈情形有關連,從共軛焦顯微鏡的結果中可看出,摻合磷脂質微小球其蛋白質螢光較少分佈於表面;反觀未摻合磷脂質微小球,其表面則較多螢光反應,因此蛋白質分佈於表面的結果造成其釋放速率的增加。 此外,從FTIR的結果同樣可以發現,在製備微小球的過程中磷脂質與PLGA有鍵結反應的現象產生,而且DSC的結果也告訴我們PLGA不僅與磷脂質有結合現象外,還具有穩定微小球於乳化過程整體結構的特性。 關鍵詞: PLGA 、乳化法、磷脂質、微小球
Abstract Phosphotydalcholine (PC) was blended with polylactide-co-glycolide (PLGA) during double (W/O/W) emulsion and solvent evaporation steps when preparing microspheres for protein delivery. This work focused on the protein profile, the possible interactions between PC and PLGA and their relates prior to PLGA being added with release profiles. The morphology for PC/PLGA microspheres showed smooth surface with less pinhole compared with that for PLGA ones. Lower protein encapsulation efficiency for PC/PLGA microspheres compared with PLGA ones was observed . It is interesting to find that encapsulation efficiency for PC/PLGA microspheres was related to polylactide (PLA) contents in PLGA matrix. The hydrophobic property of different PLA contents of PLGA and their interactions with PC could be attributed to difference in protein encapsulation efficiency. Linear and non-initial burst albumin release profiles were observed for PC/PLGA microspheres that were suitable for protein delivery. Keywords: phosphotydalcholine, polylactide-co-glycolide, protein delivery, microspheres and biomaterial
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