Investigation of the biodistribution, breakdown and excretion of delta inulin adjuvant.
Investigation of the biodistribution, breakdown and excretion of delta inulin adjuvant.
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δ菊粉佐剂的生物分布、分解和排泄的研究。
DOI：
10.1016/j.vaccine.2017.06.045
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发表时间：
2017
期刊：
影响因子：
5.5
通讯作者：
Garg,Sanjay
中科院分区：
文献类型：
--
作者：
Wang,Lixin;Barclay,Thomas;Song,Yunmei;Joyce,Paul;Sakala,IsaacG;Petrovsky,Nikolai;Garg,Sanjay
不溶性的纳米结构的δ菊粉颗粒增强共同施用的蛋白质抗原的免疫原性，因此用作疫苗佐剂（Advax™）。为了更好地了解它们的免疫调节特性，研究了δ菊粉颗粒的体外水解和体内分布。在生物相关的酸性条件下的δ菊粉颗粒水解导致使用SEM没有观察到的本体形态的变化，并且HPLC结果显示在21天内只有6.1%的菊粉被水解。然而，65%的末端葡萄糖基团被释放，表明酸水解相对快速地释放表面结合的化学物质。这用于解释体内生物分布结果，其中使用肌内（I.M.）或皮下（S.C.）航线比较分析维持在室温或加热至100 °C以溶解颗粒菊糖的均质组织上清液中可溶性菊糖的荧光，以区分可溶性菊糖上的荧光探针和与颗粒内菊糖结合的探针。在两个IM和S.C.注射δ菊粉表现出储库行为，局部注射部位停留数周。在这段时间内，随着注射部位菊粉减少，巨噬细胞向次级淋巴器官和肝脏转运了可测量的完整δ菊粉颗粒。最终，注射的δ菊粉溶解，导致其在血浆和尿液中被检测到。因此，注射的δ菊粉颗粒最初在注射部位被巨噬细胞摄取，运输到次级淋巴组织和肝脏，并水解，导致它们变得可溶并扩散到血流中，从那里它们被肾小球过滤并排泄到尿中。这些结果为了解I.M.的生物分布提供了重要见解。或S.C.当用作疫苗佐剂时注射的δ菊粉颗粒及其排泄方法。
Insoluble, nanostructured delta inulin particles enhance the immunogenicity of co-administered protein antigens and consequently are used as a vaccine adjuvant (Advax™). To better understand their immunomodulatory properties, thein vitrohydrolysis andin vivodistribution of delta inulin particles were investigated. Delta inulin particle hydrolysis under bio-relevant acidic conditions resulted in no observable change to the bulk morphology using SEM, and HPLC results showed that only 6.1% of the inulin was hydrolysed over 21 days. However, 65% of the terminal glucose groups were released, showing that acid hydrolysis relatively rapidly releases surface bound chemistries. This was used to explainin vivobiodistribution results in which delta inulin particles surface-labelled with fluorescein-5-thiosemicabizide were administered to mice using intramuscular (I.M.) or subcutaneous (S.C.) routes. Comparison analysis of the fluorescence of soluble inulin in the supernatants of homogenised tissues maintained at room temperature or heated to 100 °C to solubilise particulate inulin was used to distinguish between fluorescent probe on soluble inulin and probe bound to inulin within particles. Following both I.M. and S.C. injection delta inulin exhibited a depot behaviour with local injection site residence for several weeks. Over this time, as injection site inulin reduced, there was measurable transport of intact delta inulin particles by macrophages to secondary lymphoid organs and the liver. Ultimately, the injected delta inulin became solubilised resulting in its detection in the plasma and in the urine. Thus injected delta inulin particles are initially taken up by macrophages at the site of injection, trafficked to secondary lymphoid tissue and the liver, and hydrolysed resulting in their becoming soluble and diffusing into the blood stream, from whence they are glomerularly filtered and excreted into the urine. These results provide important insights into the biodistribution of I.M. or S.C. injected delta inulin particles when used as vaccine adjuvants and their method of excretion.
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影响因子：
5.5
作者：
Saade, Fadi;Honda-Okubo, Yoshikazu;Trec, Samay;Petrovsky, Nikolai
通讯作者：
Petrovsky, Nikolai
影响因子：
5.5
作者：
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影响因子：
5.5
作者：
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影响因子：
4.3
作者：
Cooper, Peter D.;Petrovsky, Nikolai
通讯作者：
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影响因子：
11.2
作者：
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