多孔性幾丁聚醣薄膜基質之微脂體/纖維蛋白藥控系統

Porosity chitosan membrane for controlled drug release from a liposome/fibrin system

楊明嘉(Ming-cha Yang)

指導教授 ： 陳文斌

中原大學/工學院/醫學工程研究所/碩士(2003年)

https://doi.org/10.6840/cycu200300744

摘要

微脂體(liposome)對親，疏水性藥物具有良好的攜帶性，但釋放時間快及血液中的半生期短。故研究以多孔性幾丁聚醣薄膜為基質且以纖維蛋白來穩定薄膜內的微脂體來達到延長釋放的效果，討論內容含下列：一、幾丁聚醣薄膜/微脂體-牛之纖維蛋白系統藥物釋放之特性。二、幾丁聚醣薄膜/微脂體-人類低血小板含量血漿形成纖維蛋白系統藥物釋放之特性。三、以戊二醛交聯系統內之纖維蛋白來達到延長釋放的效果。四、釋放後藥物之活性。
結果發現，以微脂體包覆螢光劑(Quinacrine)於幾丁聚醣薄膜/微脂體-牛之纖維蛋白系統比未含纖維蛋白系統，延長釋放從第3天延長到第七天，但不具降低突釋效果；若將牛之纖維蛋白換成人類低血小板含量血漿(PPP)所形成之纖維蛋白，延長釋放達7天，降低突釋達25%以上。以微脂體包覆trypsin作實驗製成之測試，仍保有藥物活性。再以微脂體包覆tirofiban於幾丁聚醣薄膜/微脂體-人類低血小板含量血漿之纖維蛋白系統，以2.5% 濃度戊二醛交聯系統內之纖維蛋白效果最好，比未使用戊二醛交聯之系統降低突釋約85%以上，延長釋放至第19天。並量測試放後tirofiban之活性測試，證明使用戊二醛後不會使tirofiban活性喪失。

關鍵字

幾丁聚醣儲槽 ； 戊二醛 ； 纖維蛋白 ； 微脂體

並列摘要

A depot drug delivery system, CFLMS, has been developed which contained only biodegradable, non-toxic and natural biomaterials. The system contained with a porous chitosan membrane with 200 慆 pore size as a reservoir for fibrin encapsulated different surface charges of liposomes for water-soluble drug delivery. Quinacrine (QR), a water-soluble fluorescent marker, was chosen as a model drug for evaluating the release characteristics of the system.
The surface charges of liposomes were consistent with the measurements of zeta potential. The encapsulation efficiency of QR was related with the particle sizes of liposomes. The releases of QR from the liposomes at 37 0C are only 2days except 3 days for negative charge ones. The release period of QR from chitosan membrane / liposome system without fibrin encapsulation were sustained about two times longer than that of QR encapsulated in liposomes only. It suggests that some interactions between liposomes and chitosan membrane to result in sustained release of QR. Interestingly, the release period of QR from CFLMS were sustained 4 times longer (e.g., 9 ~ 11 days) than those QR encapsulated in liposomes only. Enhancing sustain release of QR from CFLMS was mainly contributed by fibrin network while chitosan membrane should be also taken accounts. The mechanisms of QR release from CFLMS were mainly due to the hydrolysis of fibrin network resulted in rupture of liposome vesicles while chitosan membrane was relatively intact.
In conclusion, a depot drug delivery system, CFLMS, has been developed which can effectively sustain the release of water-soluble drug that may be further applied in different clinical fields.

並列關鍵字

fibrin ； chitosan membrance ； glutaradehyde ； liposome

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