泛影葡胺脂质体的制备及其肝脏靶向增强效应观察

The Experimental Study on the Preparation of Diatrizoate liposomes and Their Application for Liver Targeting Contrast Enhancement

目的：探讨泛影葡胺脂质体对肝脏靶向增强的可能。材料和方法：采用乙醚注射法（胆固醇与卵磷脂摩尔比１：１）制备包裹泛影葡胺的大单层脂质体；用ＣＴ观察其对大鼠肝炎型假瘤（ｎ＝４）的靶向增强效果。结果：（１）所制备的装载泛影葡胺脂质体粒径为０．８２±０．３２μｍ，面积为８．４±４．０μｍ２，体积为６．９±１．３μｍ３。造影剂包裹率为１０．１％。体外稳定试验表明泛影葡胺质体放置３ｄ时，含碘量仍保持９３．８％，７ｄ后造影剂大量渗漏，含碘量降至４１．８％。（２）泛影葡胺脂质体能靶向性分布于肝脏，使正常组织呈渐进式增强，３０ｍｉｎ达到高峰，以后逐渐下降，１２ｈ后恢复至基础水平。肝炎性假瘤灶在给药后３０ｍｉｎ显示最佳。结论：泛影葡胺脂质体能有效提高肝脏增强水平，对提高肝脏病变的显示有重要作用。

Purporse: To explore the efficiency and possibility of liposomic diatrizoate as hepatic tissue seeking contrast material in rats. ]Materials and Methods: The large unilamelar liposomes entrapped diatrizoate prepared by ether injection method (egg lecithin/cholesterol in 1:1 molar ratio). Then, The diatrizoate-carrying liposomes were intravenously injected at a dose of 30mg I/rat in 4 rates with pseudo hepatic tumor induced by local injection of Freund' complete adjuvant. The contrast enhancing degree of the liver was evaluated with computed tomography. Results: The diatroziate loading liposomes made here ranged 0.82+0.32 m in diameter, 8.4+4.0m2 in area, 6.9+1.3m3 in volume. The encapsulation efficiency was 10.1%.The stability of the vesicle was determined by means of dialysis. We found 93.8% of iodine remained inside the liposome suspension which stored at 4 for 3 days, while only 418% of iodine left in the liposomes over 7 days. After injection of the liposomes, the normal hepatic tissue show density rise over the next 15 minutes. The maximal enhancement in the liver was reached 30 minutes after injection of the contrast. The liver opacity was gradually decreased over the 60 minutes. Finally, the baseline level was obtained 12 hours after administration of the liposomes. The hepatic pseudotumor lesions were best demonstrated 30 minutes after the injection. Z]Conclusion: The diatroziate-loading liposomes can effectively chang the biodistribution of the diatroziate and results in specifically hepatic uptake. It may improve the detection of small lesions in liver.