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  • 學位論文

溶媒添加對擠壓成形法製備微脂體包覆藥物之影響與評估

Evaluation of drug encapsulation with liposome prepared by extrusion via additive solvent

指導教授 : 孫一明

摘要


評估利用添加乙醇對擠壓成形法製備藥物載體「微脂體」包覆杜薩魯比辛(doxorubicin)的影響以改進微脂體關鍵製作步驟為本文所要探討的目的。 本研究利用有機溶媒可以降低微脂體混懸液表面張力與黏度的基本作用,設計一系列含有不同比例有機溶媒的緩衝溶液,使用適當孔徑的濾膜以獲得理想的擠壓過濾壓力以及流速;而對於這些測試樣品則分別針對微脂體粒徑、有機溶媒殘餘量、磷脂質濃度存留、藥物包覆率等指標項目進行樣品的分析,確認樣品的品質符合基本微脂體的要求。 隨著乙醇比例的增加,擠壓流速增加、擠壓壓力下降,但是當乙醇比例增加至超過50%以上時則會有磷脂質於製作過程中流失之疑慮,以及磷脂質流失後所帶來的藥物包覆率降低的問題,乙醇與緩衝液體積百分比為30%(V/V)時為最佳的微脂體奈米化參數。

關鍵字

微脂體

並列摘要


Object of this article was focus on the critical step, particle size reduction, to gear up the process of manufacture drug carrier vehicle “liposome”. And the additive ethanol solvent could dramatically speed up the flow rate and lower resisted pressure in extrusion process. Base on the principle, organic solvents can both reduce surface tension and viscosity of lipid suspension, design a series of different ratio of ethanol containing buffer solution to form liposome vehicle with extrusion method. The final sample will be analyzed following the criteria: particle size, residual solvent, phospholipids concentration, total drug concentration and encapsulation ratio. The experiment sample will be qualified when they met the requirements. According to the result, with the increase in the proportion of ethanol, raised flow rate up of liposome suspension, lower resisted pressure of extrusion. When the proportion of ethanol was over 50 percent of the sample solution will result phospholipid in the production process of loss concerns. And lower phospholipid concentration brought the loss of encapsulation ratio. The optimized ratio of ethanol to buffer solution was 30 % (V/V) to manufacture liposome product.

並列關鍵字

liposome

參考文獻


Dibiase S.J., L.S. Chin, and L. Ma, “Influence of Gamma Knife Radiosurgery on thr Quality of Life in Patients with Brain Metastases,” American Journal of Clinical Oncology, 25(2002) 131 – 134.
Schuller J., M. Czejka, S. Bandak, D. Borow, C. Pietrzak, I. Marei, and G. Schernthaner, “Comparison of pharmacokinetics of free and liposome encapsulated doxorubicin in advanced cancer patients,” European Journal of Cancer, 31(1995) 199 – 203.
Akeuchi H.T., H.K. Ojima, H.Y. Amamoto, and Y.K. Awashima, “Passive Targeting of Doxorubicin with polymer coated liposomes in Tumor Bearing Rats,” Biol. Pharm. Bull., 24(2001)795 – 799.
Bangham A. D., M. M. Standish, J. C. Watkins, “Diffusion of Univalent Ions across the Lamellae of Swollen Phosopholipids,” Journal of Molecular Biology, 13(1965) 238 – 252.
Pick U., “Liposomes with a Large Trapping Capacity Prepared by Freezing and Thawing of Sonicated Phospholipid Mixtures,” Arch. Biochem. Biophys., 212(1981) 186 – 194.

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