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Fibrin gels entrapment of a doxorubicin-containing targeted polycyclodextrin: Evaluation of in vivo antitumor activity in orthotopic models of human neuroblastoma.
Toxicology and Applied Pharmacology ( IF 3.8 ) Pub Date : 2019-11-06 , DOI: 10.1016/j.taap.2019.114811 Maurizio Viale 1 , Graziella Vecchio 2 , Irena Maric 1 , Michele Cilli 3 , Anna Aprile 4 , Mirco Ponzoni 5 , Vincenzo Fontana 6 , Erica C Priori 7 , Vittorio Bertone 8 , Mattia Rocco 4
Toxicology and Applied Pharmacology ( IF 3.8 ) Pub Date : 2019-11-06 , DOI: 10.1016/j.taap.2019.114811 Maurizio Viale 1 , Graziella Vecchio 2 , Irena Maric 1 , Michele Cilli 3 , Anna Aprile 4 , Mirco Ponzoni 5 , Vincenzo Fontana 6 , Erica C Priori 7 , Vittorio Bertone 8 , Mattia Rocco 4
Affiliation
In vivo local antitumor activity of fibrin gels (FBGs) loaded with the poly-cyclodextrin oCD-NH2/Dox, compared to free Dox, was evaluated in two mouse orthotopic neuroblastoma (NB) models, after positioning of the releasing devices in the visceral space. FBGs were prepared at the fibrinogen (FG) concentrations of 22 and 40 mg/ml clotted in the presence of 0.81 mM/mg FG Ca2+ and 1.32 U/mg FG thrombin. Our results indicate that FBGs loaded with oCD-NH2/Dox and applied as neoadjuvant loco-regional treatment, show an antitumor activity significantly greater than that displayed by the same FBGs loaded with identical dose of Dox or after free Dox administered intra venous (iv). In particular, FBGs prepared at 40 mg/ml showed a slightly lower antitumor activity, although after their positioning we observed a significant initial reduction of tumor burden lasting for several days after gel implantation. FBGs at 22 mg/ml loaded with oCD-NH2/Dox and applied after tumor removal (adjuvant treatment model) showed a significantly better antitumor activity than the iv administration of free Dox, with 90% tumor regrowth reduction compared to untreated controls. In all cases the weight loss post-treatment was limited after gel application, although in the adjuvant treatment the loss of body weight lasted longer than in the other treatment modality. In accordance with our recent published data on the low local toxic effects of FBGs, the present findings also underline an increase of the therapeutic index of Dox when locally administered through FBGs loaded with the oCD-NH2/Dox complex.
中文翻译:
含有阿霉素的靶向多环糊精的纤维蛋白凝胶截留:在人类神经母细胞瘤原位模型中评估体内抗肿瘤活性。
与释放Dox相比,负载了多环糊精oCD-NH2 / Dox的纤维蛋白凝胶(FBG)的体内局部抗肿瘤活性在释放装置定位于内脏空间的两个小鼠原位神经母细胞瘤(NB)模型中进行了评估。在纤维蛋白原(FG)浓度为22和40 mg / ml的条件下,在0.81 mM / mg FG Ca2 +和1.32 U / mg FG凝血酶存在的条件下凝结制备FBG。我们的结果表明,负载oCD-NH2 / Dox并用作新辅助局部治疗的FBG,其抗肿瘤活性显着大于负载相同剂量Dox或静脉注射游离Dox后的相同FBG的抗肿瘤活性(iv)。 。特别是,以40 mg / ml的浓度制备的FBG的抗肿瘤活性略低,尽管在他们定位之后,我们观察到了凝胶植入后几天持续数天的肿瘤负担的显着初始减少。载有oCD-NH2 / Dox的22 mg / ml FBGs在切除肿瘤后应用(辅助治疗模型)显示出比静脉给予游离Dox显着更好的抗肿瘤活性,与未治疗的对照组相比,其肿瘤再生长减少了90%。在所有情况下,凝胶施涂后治疗后的体重减轻均受到限制,尽管在辅助治疗中体重减轻的持续时间长于其他治疗方式。根据我们最近发表的有关FBG的低局部毒性作用的数据,本发现还强调了当通过载有oCD-NH2 / Dox复合物的FBG局部给药时,Dox的治疗指数增加。
更新日期:2019-11-06
中文翻译:
含有阿霉素的靶向多环糊精的纤维蛋白凝胶截留:在人类神经母细胞瘤原位模型中评估体内抗肿瘤活性。
与释放Dox相比,负载了多环糊精oCD-NH2 / Dox的纤维蛋白凝胶(FBG)的体内局部抗肿瘤活性在释放装置定位于内脏空间的两个小鼠原位神经母细胞瘤(NB)模型中进行了评估。在纤维蛋白原(FG)浓度为22和40 mg / ml的条件下,在0.81 mM / mg FG Ca2 +和1.32 U / mg FG凝血酶存在的条件下凝结制备FBG。我们的结果表明,负载oCD-NH2 / Dox并用作新辅助局部治疗的FBG,其抗肿瘤活性显着大于负载相同剂量Dox或静脉注射游离Dox后的相同FBG的抗肿瘤活性(iv)。 。特别是,以40 mg / ml的浓度制备的FBG的抗肿瘤活性略低,尽管在他们定位之后,我们观察到了凝胶植入后几天持续数天的肿瘤负担的显着初始减少。载有oCD-NH2 / Dox的22 mg / ml FBGs在切除肿瘤后应用(辅助治疗模型)显示出比静脉给予游离Dox显着更好的抗肿瘤活性,与未治疗的对照组相比,其肿瘤再生长减少了90%。在所有情况下,凝胶施涂后治疗后的体重减轻均受到限制,尽管在辅助治疗中体重减轻的持续时间长于其他治疗方式。根据我们最近发表的有关FBG的低局部毒性作用的数据,本发现还强调了当通过载有oCD-NH2 / Dox复合物的FBG局部给药时,Dox的治疗指数增加。