Anti-Angiogenic Effects of Betulinic Acid Administered in Nanoemulsion Formulation Using Chorioallantoic Membrane Assay
Anti-Angiogenic Effects of Betulinic Acid Administered in Nanoemulsion Formulation Using Chorioallantoic Membrane Assay
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DOI：
10.1166/jbn.2011.1297
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发表时间：
2011-04-01
影响因子：
2.9
通讯作者：
Amiji, Mansoor
中科院分区：
文献类型：
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作者：
Dehelean, Cristina A.;Feflea, Stefana;Amiji, Mansoor
桦木酸（3 β，hydroxy-lup-20（29）-en-28-oic acid，BA）是一种五环三萜类化合物，来源于广泛分布的天然抗癌化合物桦木醇。它对几种肿瘤细胞具有选择性抗癌活性，最近显示它也具有抗血管生成作用。本研究的目的是将桦木酸（一种水溶性差的化合物）配制在含有亚麻籽油的纳米乳液制剂中，以提高递送效率并有效抑制肿瘤血管生成过程。使用高压均质化方法用Microfludizer（R）处理器制备纳米乳液。通过进行体内鸡胚绒毛尿囊膜（CAM）测定来研究桦木酸纳米乳对血管生成过程的影响。将样品体积为1 μ l和5 μ l的空白和BA纳米乳剂直接施加到CAM上。肉眼、形态学和免疫组织化学评价的初步结果表明，CAM间充质中产生了形态学变化，对毛细血管的正常生长产生了负面影响。桦木酸确实以剂量依赖性方式具有抗血管生成活性，并且纳米乳液制剂保持了这种效果。
Betulinic acid (3 beta, hydroxy-lup-20(29)-en-28-oic acid, BA), a pentacyclic triterpenoid, is derived from a widely distributed natural anticancer compound betulin. It has selective anticancer activity against several tumor cells, and recently it was shown that it also possess anti-angiogenic effects. The objective of this study was to formulate betulinic acid, a poorly aqueous-soluble compound, in flax-seed oil containing nanoemulsion formulation for enhanced delivery efficiency and to effectively inhibit the tumor angiogenic process. The nanoemulsion was prepared using high pressure homogenization method with a Microfludizer (R) processor. The betulinic acid nanoemulsion was studied for the effect on the angiogenic process by performing the in vivo chick embryo chorioallantoic membrane (CAM) assay. The sample volume of 1 mu l and 5 mu l of the blank and BA nanoemulsions were applied directly on the CAM. The preliminary results from macroscopic, morphological and immunohistochemical evaluations have shown that morphological change was produced in the CAM mesenchyme with a negative impact on the normal growth of the capillaries. Betulinic acid does possess anti-angiogenic activity in a dose dependent manner, and the nanoemulsion formulation maintained this effect.