萜類化合物euphol微脂粒製劑 之處方設計與活性評估

Formulation design and bioactivity evaluation of liposomal dosage form of euphol

吳瑋強(Wei-Chiang Wu)

指導教授 ： 吳寶珠

高雄醫學大學/藥學院/藥學研究所/碩士(2013年)

摘要

Euphol為具有抑制胃癌細胞活性之水難溶性三萜類化合物。為改善其溶解度與刺激性，並增加藥物活性效益，本研究主要利用微脂粒劑型作為藥物包覆載體，依據其粒徑分佈大小、均勻分散度、zeta電荷、包埋率、外觀及貯存安定性進行處方設計之物化性質評估。此外亦以MKN45和CS12胃癌細胞株進行細胞毒性之測試，進而篩選出理想處方，並同時對其作用路徑作初步探討。本研究結果顯示，以Epikuron-200/cholesterol/stearylamine = 8/1/0.1為脂質相，1% Tween 80為水相所製備而成的帶正電荷微脂粒處方，其粒子大小約在75~85 nm間，包埋率可高達接近完全包覆，外觀澄清透明且具備良好之物化安定性。在細胞毒殺能力測試中，與同濃度溶液劑和不帶電微脂粒處方比較後，則顯示出其為最適當且更具抑制胃癌細胞活性之微脂粒處方。此外，而在作用路徑方面，根據胃癌細胞膜萃取實驗和利用生物分子交互作用分析系統(Biacore 3000)對細胞膜親和力之測定，推測euphol為極容易與細胞膜結合而作用之天然物。

關鍵字

大戟醇 ； 正電荷微脂粒 ； 胃癌細胞 ； 細胞毒性

並列摘要

Euphol is a water-insoluble triterpene compound which exhibits the inhibition activity for gastric cancer cell. The purpose of this study was to develop the optimal liposome formulation as a carrier to overcome the poor solubility as well as irritation, and improve the efficiency of euphol. The liposomal dosage form after formulation designing was screened by particle size, polydispersity index, zeta potential, encapsulation efficiency, the image of appearance using TEM and stability. Besides, the bioactivity of formulations was evaluated using MKN45 and CS12 cell viability. At the same time, we also discussed and found the pathway of euphol. The results were shown that the positive-charge liposome formulations containing Epikuron-200/cholesterol/stearylamine = 8/1/0.1 as lipid phase, 1% Tween 80 as water phase had clear appearance and good physicochemical stability. The particle size was about 75~85 nm and the encapsulation rate was almost 100%. Compare to the same concentration solution type and non-charge liposome formulations of euphol, it had the best inhibition activity to gastric cancer cell line. In addition, according to the extraction of gastric cancer cell membrane and affinity detection by the Biacore 3000 interaction analysis system, we inferred that euphol was a drug combining cell membrane easily.

並列關鍵字

euphol ； positive-charge liposome ； gastric cancer cell line ； cell viability

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