Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.
Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.
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DOI：
10.1371/journal.pone.0102329
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Eckmann DM
中科院分区：
文献类型：
--
作者：
Ferrer MC;Shuvaev VV;Zern BJ;Composto RJ;Muzykantov VR;Eckmann DM
溶菌酶葡聚糖纳米凝胶（NG）在体外作为药物递送平台具有巨大的潜力，其将简单的化学与靶细胞中的快速摄取和货物释放相结合，具有“隐身”性质和低毒性。在这项工作中，我们首次研究了靶向NG作为体内药物递送平台的潜力，以减轻LPS诱导的肺损伤动物模型中的急性肺部炎症。NG通过与针对细胞间粘附分子-1（ICAM-NG）的抗体（Ab）缀合而靶向内皮，而IgG缀合的NG（IgG-NG）用于对照制剂。使用示踪同位素标记的[125 I]IgG定量分析了静脉（IV）注射后与NG结合的Ab量和体内分布。作为概念的证明，Ab-NG装载有地塞米松（一种抗炎治疗剂），并且通过HPLC测量药物摄取和释放动力学。小鼠体内研究显示：i）ICAM-NG在小鼠肺中积累（约120%ID/g对约15%ID/g的IgG-NG）;和ii）包封在ICAM-NG中但不包封在IgG-NG中的DEX实际上阻断LPS诱导的促炎细胞粘附分子（包括肺部炎症中的ICAM-1）的过表达。
Lysozyme dextran nanogels (NG) have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with “stealth” properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a drug delivery platform in vivo to alleviate acute pulmonary inflammation in animal model of LPS-induced lung injury. NG are targeted to the endothelium via conjugation with an antibody (Ab) directed to Intercellular Adhesion Molecule-1(ICAM-NG), whereas IgG conjugated NG (IgG-NG) are used for control formulations. The amount of Ab conjugated to the NG and distribution in the body after intravenous (IV) injection have been quantitatively analyzed using a tracer isotope-labeled [125I]IgG. As a proof of concept, Ab-NG are loaded with dexamethasone, an anti-inflammatory therapeutic, and the drug uptake and release kinetics are measured by HPLC. In vivo studies in mice showed that: i) ICAM-NG accumulates in mouse lungs (∼120% ID/g vs ∼15% ID/g of IgG-NG); and, ii) DEX encapsulated in ICAM-NG, but not in IgG-NG practically blocks LPS-induced overexpression of pro-inflammatory cell adhesion molecules including ICAM-1 in the pulmonary inflammation.
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影响因子：
5.7
作者：
Henzi, I;Walder, B;Tramèr, MR
通讯作者：
Tramèr, MR
用于血管输送抗炎剂的纳米载体。
DOI：
10.1146/annurev-pharmtox-011613-140002
发表时间：
2014
影响因子：
12.5
作者：
Howard MD;Hood ED;Zern B;Shuvaev VV;Grosser T;Muzykantov VR
通讯作者：
Muzykantov VR
影响因子：
4.6
作者：
Chittasupho, Chuda;Xie, Sheng-Xue;Baoum, Abdulgader;Yakovleva, Tatyana;Siahaan, Teruna J.;Berkland, Cory J.
通讯作者：
Berkland, Cory J.
影响因子：
3.4
作者：
Ferrer MC;Hickok NJ;Eckmann DM;Composto RJ
通讯作者：
Composto RJ
影响因子：
3.4
作者：
Armstrong, JK;Wenby, RB;Fisher, TC
通讯作者：
Fisher, TC