幾丁聚醣-果膠複合材料微粒之製備、特性分析及應用探討

Abstract

本研究嘗試將兩種天然多醣類高分子幾丁聚醣 (chitosan) 與果膠 (pectin) 進行結合形成複合材料，並將其製備成微粒，以探討此種複合材料微粒在藥物控制釋放上對於負載大分子藥物的應用潛力。 在以乳化法進行幾丁聚醣-果膠複合材料微粒的製程中發現，Tween 81製備出的複合材料微粒有餃小的粒徑和較集中的分布，適合用於做為此系統的界面活性劑。而在固定複合材料微粒時，以 NaOH/乙醇水溶液處理 1 小時即可以達到有效的固定。另外分散相的濃度越大產量會越大。而複合材料微粒的粒徑隨著混合的重量比越接近粒徑也越大。 在成功製備出幾丁聚醣-果膠複合材料微粒後，利用 FTIR 和 DSC 檢測其分子間的作用力，證實幾丁聚醣-果膠兩者之間作用力的存在。接著以 SHED 細胞的培養來測試複合材微粒的細胞毒性，結果顯示沒有明顯的毒性。在複合材料微粒之吸水能力實驗中，發現複合材料微粒的吸水能力隨果膠比例越高而越好。而在溶蝕特性實驗中，發現複合材料微粒隨組成比例的不同在不同酸鹼性環境下的溶蝕表現也會不同。之後以 BSA 進行模擬大分子藥物承載及釋放實驗，結果發現幾丁聚醣-果膠複合材料微粒可以有效的控制 BSA 在不同 pH 值環境下的釋放效果，其結果也呼應著複合材料微粒的溶蝕特性結果。此外，BSA 的承載率也因為複合材料微粒的使用而增加。 本研究以幾丁聚醣-果膠複合材料進行微粒製備並探討其在藥物控制釋放上的應用。成功的增加了 BSA 的承載率並藉由控制複合材料的組成比例以調控 BSA 在酸性環境及弱鹼性環境的釋放速率，顯示複合材料微粒具有在藥物控制釋放上的應用潛力。

In this study, chitosan and pectin, two kinds of natural polysaccharide were combined to fabricate chitosan-pectin composite microparticles by emulsion method. The characteristics and potential applications of the composite microprticles as drug delivery carriers were also investigated. First, the effects of various operating parameters for emulsion were studied. The results of size analysis showed that the microparticles prepared using surfactant Tween 81 had smaller size. To fix the microparticles, 1 hour of NaOH treatment time was sufficient without changing the size distributions of microparticles. As the total concentration of disperse phase (chitosan-pectin mixture solutions) increased, the yield of microparticles increased. The properties were further characterized of chitosan-pectin composite microparticles. The DSC results suggested that the interaction between chitosan and pectin did exist. The results of FTIR implied the presence of the interaction between amino groups of chitosan and carboxyl groups of pectin. Besides, according to the results of cell culture and MTT assay, the composite microparticles showed almost no cytotoxicity. The water-uptake capacity of composite microparticles increased as the ratio of chitosan to pectin increased. The erosion test showed that the erosion properties of composite mircroparticles were adjustable by altering the composition of microparticles. Finally, using BSA as a model drug, the encapsulation efficiency and release profile of BSA in the microparticles were measured. The results showed that enhanced encapsulation efficiency was achieved by using the composite microparticles. We also found that the more chitosn present in the microparticles, the faster the BSA released under acidic conditions. In contrast, the more pectin present in the microparticles, the faster the BSA released under basic conditions. In brief, the chitosan-pectin composite microparticles were prepared by emulsion method. The composite microparticles showed better encapsulation property, and adjustable BSA release profiles. The chitosan-pectin composite microparticles therefore have application potential in controlled release of drugs.