Pharmacokinetics of a paclitaxel-loaded low molecular weight heparin-all-trans-retinoid acid conjugate ternary nanoparticulate drug delivery system
Pharmacokinetics of a paclitaxel-loaded low molecular weight heparin-all-trans-retinoid acid conjugate ternary nanoparticulate drug delivery system
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负载紫杉醇的低分子量肝素-全反式-维A酸缀合物三元纳米颗粒药物递送系统的药代动力学
DOI：
10.1016/j.biomaterials.2012.03.070
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发表时间：
2012-07-01
期刊：
影响因子：
14
通讯作者：
Zhang, Qiang
中科院分区：
文献类型：
--
作者：
Hou, Lin;Yao, Jing;Zhang, Qiang
我们先前的研究发现，两亲性低分子肝素-全反式维甲酸(LHR)结合物作为癌症治疗的药物载体，具有明显的低毒性，并形成自组装纳米粒，用于同时传递紫杉醇(PTX)和全反式维甲酸(ATRA)。在本研究中，制备了PTX负载的LHR纳米颗粒，其颗粒尺寸为108.9 nm，呈球形。细胞摄取分析表明LHR纳米颗粒迅速内化和核转运。为了研究LHR纳米粒子在荷瘤小鼠体内的动态行为和靶向能力，将近红外荧光染料DIR包裹到纳米粒子中进行体外光学成像。结果表明，LHR纳米粒可提高靶向性和在肿瘤部位的滞留时间。此外，体内生物分布研究还表明，PTX和ATRA纳米粒在肿瘤中的血药浓度时间曲线下面积(AUC(0->；inf))分别是PTX+ATRA溶液的1.56和1.62倍。最后，与PTX溶液和FIX+ATRA溶液相比，PTX负载的LHR纳米粒在体内显示出更强的肿瘤生长抑制作用，且没有意外的副作用。这些结果表明，载PTX的LHR纳米粒有望成为肿瘤联合化疗的靶向给药系统，以提高治疗效果，减少不良反应。(C)2012爱思唯尔有限公司。保留所有权利。
Amphiphilic low molecular weight heparin-all-trans-retinoid acid (LHR) conjugate, as a drug carrier for cancer therapy, was found to have markedly low toxicity and to form self-assembled nanoparticles for simultaneous delivery of paclitaxel (PTX) and all-trans-retinoid acid (ATRA) in our previous study. In the present study, PTX-loaded LHR nanoparticles were prepared and demonstrated a spherical shape with particle size of 108.9 nm. Cellular uptake analysis suggested rapid internalization and nuclear transport of LHR nanoparticles. In order to investigate the dynamic behaviors and targeting ability of LHR nanoparticles on tumor-bearing mice, near-infrared fluorescent (NIFR) dye DiR was encapsulated into the nanoparticles for ex vivo optical imaging. The results indicated that LHR nanoparticles could enhance the targeting and residence time in tumor site. Furthermore, in vivo biodistribution study also showed that the area under the plasma concentration time curve (AUC (0 -> inf)) values of PTX and ATRA for PTX-loaded LHR nanoparticles in tumor were 1.56 and 1.62-fold higher than those for PTX plus ATRA solution. Finally, PTX-loaded LHR nanoparticles demonstrated greater tumor growth inhibition effect in vivo without unexpected side effects, compared to PTX solution and FIX plus ATRA solution. These results suggest that PTX-loaded LHR nanoparticles can be considered as promising targeted delivery system for combination cancer chemotherapy to improve therapeutic efficacy and minimize adverse effects. (C) 2012 Elsevier Ltd. All rights reserved.