- 學位論文
探討承載克霉唑之脂質載體對局部白色念珠菌感染的抗真菌效果
Evaluation of the antifungal efficacy of Clotrimazole loaded lipid based formulation against topical Candida albicans infection
摘要
白色念珠菌 (Candida albicans) 為念珠菌屬中的一種微生物，是人體內常見的伺機性病原菌之一。有研究指出白色念珠菌所造成的死亡率大約是四成，目前主要的治療方法為使用抗真菌劑治療。而作為念珠病感染的局部第一線用藥克霉唑 (Clotrimazole, CTZ) 是唑類抗真菌藥物中的一種，屬於親脂性藥物，溶解度的問題限制了其在抗真菌治療的應用。CTZ在目前市售產品及文獻中，主要是藉由能承載親脂性藥物的遞送載體，如：油膏 (ointment) 或是乳膏 (cream) 等。這些較為油膩的製劑容易造成患者產生不適感，或是因所添加之賦形劑 (excipient) 產生過敏反應等。本研究藉由實驗室先前發展的脂質載體來進行CTZ的劑型改良。實驗結果發現改良的新劑型不僅於嚴苛環境下仍保持良好的穩定性外，其藥物最大承載量甚至可比市售產品高出10倍。此外，將CTZ新劑型與CTZ loaded DMSO相比，也可發現新劑型的最小抑菌濃度MIC50能降低4倍。接著，於紙錠擴散法實驗結果得知，新劑型不論是作用於白色念珠菌、熱帶念珠菌或是兩者之抗藥性菌株上，皆具有比市售乳膏產品更好的抑菌效果，顯示了CTZ新劑型具有多元的應用價值。而在生物膜形成的試驗中，也發現了CTZ新劑型不僅能降低白色念珠菌生物膜生成的能力，於高濃度之下也能破壞較為完整的生物膜結構。綜合上述，本研究發現CTZ新劑型在各項抑菌試驗中皆表現優異，具有良好的發展潛力。
並列摘要
Fungal Candida albicans belongs to genus of Candida, which is one of the most common opportunistic pathogens in the human body. Present studies showed the mortality rate caused by C. albicans is about 40%, and currently the main treatment is using antifungal agents. Clotrimazole (CTZ), the first-line drug for Candida infections, is one of the azole antifungal drugs. Presently, the main dosages form used for CTZ are ointment or cream. However, these relatively greasy preparations may cause discomfort or allergic reactions due to the utilization of excipients. In this study, CTZ was prepared using lipid base formulation developed in our laboratory. The experimental results showed the lipid based CTZ formula not only had better stability under harsh conditions, but had a drug loading capacity 10 times higher than CTZ commercial products. The minimum inhibitory concentration (MIC50) of the new formulation was 4 times lower than CTZ dissolved in DMSO. Meanwhile, the results of the disk diffusion assay showed the new formulation was more effective than CTZ commercial cream in inhibiting C. albicans, C. tropicalis, and resistant strains of both, indicating the diverse applications of new formulation. In the biofilm formation test, we found that this CTZ formulation not only reduced the ability of C. albicans biofilm formation, but destroyed the intact biofilm structure at high drug concentration. Therefore, this study indicated that the new lipid-based CTZ formula had superior performance and good development potential.