以Caco-2細胞模式探討不同脂質微脂粒包覆低口服吸收率藥物之通透影響

EVALUATION OF THE PERMEABILITY OF DIFFERENT LIPOSOME-ENCAPSULATED LOVASTATIN BY APPLICATION OF THE CACO-2 MODEL

蘇大智(Tai-Chih Su)

指導教授 ： 顏聰榮

大同大學/工程學院/生物工程學系所/碩士(2008年)

摘要

Caco-2細胞在多聚碳酸酯膜(polycarbonate membrane)上培養可自行發生分化成具有人腸道上皮細胞相同的致密細胞單層，Caco-2細胞模式克服了整體動物吸收代謝耗藥量大的缺點，而它所要的檢測週期也較短，所以可用來作為腸胃道吸收藥物的篩選工具。微脂粒具有包覆脂溶性或水溶性藥物的特性，具有良好的生物相容性(compatible)及生物分解性(biodegradable)、無免疫反應的問題因此可用來作為藥物載體。本研究是先以DMPC(Dimyristoyl-sn-Glycero- 3-Phosphocholine)或EYPC(Egg-yolk
L-α-Phosphatidylcholine)來製成包覆的低口服吸收率藥物Lovastatin的微脂粒，再利用Caco-2細胞模式來測試藥物的通透實驗。並將對微脂粒進行粒徑分析、包覆率分析、細胞毒性分析及藥物通透測試分析。將未包覆藥物的微脂粒與Caco-2細胞進行共培養並未發現明顯的細胞毒性。經由HPLC分析儀分析後發現，當脂質與藥物比例為1：0.25(mol)時DMPC微脂粒平均包覆率為95.2 ± 0.54(％)較優於EYPC微脂粒的86.76 ± 4.71 (％)。將製備好的Lovastatin微脂粒與Lovastatin原型藥以Caco-2細胞所形成的單層膜進行通透測試後發現，DMPC與EYPC微脂粒組的藥物通透率皆高於原型藥有5.62倍及5.9倍。

關鍵字

低口服吸收率 ； 微脂粒 ； 大腸癌細胞

並列摘要

Caco-2 cells cultured on polycarbonate membrane can be spontaneously differentiated to close cell monolayer which is the same as gastrointestinal epithelial cells. Caco-2 cells as a model system can conquer the defects of using a lot of drugs for absorption and metabolism of animals. Hence, they can be used for sifting application of medicine which is absorbed in gastrointestinal tracts. Liposomes have some properties, such as good biocompatibility biodegradation, anti-immunization, and can be used for encapsulation of fat-soluble and water-soluble drug. Hence, they can be good carriers for drug delivery. In this study, liposomes for lavastatin was made by DMPC (Dimyristoyl-sn-Glycero-3-Phosphocholine) or EYPC (Egg-yolk L-α-Phosphatidylcholine) and permeation test of lovastatin by Caco-2 as a model system was studied. The vesicle volume distribution, entrapment efficiency, and cytotoxicity were analyzed and drug permeation studies through the Caco-2 cell were studied. Lipsomes were co-cultured with Caco-2 cells and significant cytotoxicity was not found. It is found that the entrapment efficiency of DMPC liposomes is 95.2 ± 0.54 (％), and EYPC liposomes is 86.76 ± 4.71 (％) when the lipids and the drugs got a ratio of 1:0.25 (mol) via HPLC Analyzer. The drug permeation of DMPC and EYPC liposomes through a monolayer made by Caco-2 cells are 5.62 and 5.9 times better than the permeation of pure drug . The result was tested using the lipsomes made by lovastatin and pure drug of lovastatin going through a monolayer made by Caco-2 cells.

並列關鍵字

Permeability of different ； Liposome ； CACO-2

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