紫質鎝錯化合物Cremophor micelles的製備及其生物分布的研究

The study of the preparation and biodistribution of ^(99m)Tc-TPPBs Cremophor micelles

王愛義(Ai-Yih Wang) ； 林昀蓉(Yung-Rong Lin) ； 王蓉敏(Rong-Min Wang) ； 陳美慧(Mei-Hui Chen) ； 黃敏鳳(Min-Feng Huang) ； 林文傑(Wen-Jye Lin)

《加馬》 49期 (2018/11) Pp. 9-15

摘要

脂質體為一雙層脂肪包覆水溶液核心所形成的圓球，它是最常見且經過充分研究減少系統毒性，用於靶向藥物遞送的納米載體。他們透過穩定治療化合物、克服細胞和組織攝取的障礙，改善化合物在體內標靶的生物分佈，為生物醫學應用開發一系列的治療方法。本論文的主要目的即是以帶羧基的卟吩（porphine），4',4＂,4＂'－（2lH,23H－Porphine－5,10,15,20－terayl）tetrakis－（benzoic acid）,TPPB）為配位子，利用^(99m)Tc為示蹤劑，氯化亞錫為還原劑，進行紫質鎝錯合物（^(99m)Tc－TPPBs）的製備，再利用Cremophor EL做為紫質鎝錯化物的載體，進行紫質鎝錯化物Cremophor micelles化學特性與生物分布的研究。從實驗結果可發現不論利用機械法（超音波震盪法）或迴旋縮法製備的紫質鎝錯化合物Cremophor溶液，以雷射粒徑分析儀分析得知均為真溶液，不會有任何脂肪微粒的產生；以濾紙電泳動分析紫質鎝錯化物Cremophor活度約為33%。在生物分布實驗中，可發現胃為靶的器官，在注射10分鐘後胃部每克組織約為注射活度3.2%（3.20% ID/g）。組織對血液的活度比亦會隨著時間增加有顯著的增加，組織對血液的活度比在注射10分鐘後約為1.31 ±0.31，經過90分鐘組織對血液的活度比增加為9.62 ± 1.21。

關鍵字

紫質 ； 鎝紫質錯合物 ； Cremophor ； 化學特性 ； 生物分布

並列摘要

Liposomes are spherical vesicles of concentric lipid bilayers around an aqueous core, there are the most common and well-investigated nanocarriers for targeted drug delivery for minimizing systemic toxicity. They have improved therapies for arrange of biomedical applications by stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites, developing a series of treatments methods for biomedical applications. The aim of this research is to use porphine {4',4＂,4＂'-(2lH,23H-Porphine-5,10,15,20-terayl) tetrakis-(benzoic acid), TPPB} as a ligand, ^(99m)Tc as a tracer, stannous chloride as a reductant¸ to prepare the ^(99m)Tc-porphyrin complex (^(99m)Tc-TppBs), then used Cremophor EL as a carrier to evaluate its chemical and biological characteristics. From the results of chemical characteristics, it can be found that the ^(99m)Tc-TppBs Cremophor solution neither (^(99m)Tc-TppBs -CrEL) prepared by mechanical method (sonication) nor by rotary evaporator method, it is a true solution analyzed by laser particle size analyzer. From the result of paper electrophoresis the activity of ^(99m)Tc-TPPBs -CrEL was 33%. In the biodistribution study, the stomach was the major target organ, approximated 3.20% of injected radioactivity dose accumulate in per gram of tissue (3.20% ID/g) at 10 min after injection. The tissue-to-blood radioactivity ratio significant (p＜0.05) increased with reaction time. In the stomach, the tissue to-blood radioactivity ratio was 1.31 ± 0.31 at 10 min after injection, and increased to 9.62 ± 1.21 at 90 min after injection.

並列關鍵字

porphyrin ； Tc-porphyrin complex ； Cremophor ； chemical characterization ； biodistribution