Design of smart GE11-PLGA/PEG-PLGA blend nanoparticulate platforms for parenteral administration of hydrophilic macromolecular drugs: synthesis, preparation and in vitro/ex vivo characterization
Design of smart GE11-PLGA/PEG-PLGA blend nanoparticulate platforms for parenteral administration of hydrophilic macromolecular drugs: synthesis, preparation and in vitro/ex vivo characterization
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DOI：
10.1016/j.ijpharm.2016.08.011
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发表时间：
2016-09-25
影响因子：
5.8
通讯作者：
Genta, Ida
中科院分区：
文献类型：
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作者：
Colzani, Barbara;Speranza, Giovanna;Genta, Ida
亲水大分子药物的活性靶向和控释是设计高效高分子给药纳米平台的关键。在本研究中，用两种不同的聚乳酸基聚合物共混制备了靶向egfr的聚乳酸-共聚物（PLGA）纳米颗粒。第一个是GE11-PLGA，其中PLGA被GE11功能化，GE11是一种小肽和EGFR变构配体，能够赋予纳米颗粒选择性靶向特性。第二种聚合物是聚乙二醇化PLGA (PEG-PLGA)，旨在提高纳米颗粒的亲水性和隐身性能。采用简单、廉价的方法合成了GE11和GE11- plga。利用纳米沉淀法制备了GE11-PLGA和PEG-PLGA重量比为1:1的聚合物纳米颗粒，获得了适合肠外给药尺寸（143.9 +/- 5.0 nm）的智能纳米平台。egfr过表达细胞系（A549）的体外细胞摄取显示了ge11功能化纳米颗粒的积极内化。GE11-PLGA/PEG-PLGA共混纳米颗粒被肌红蛋白（一种模型亲水性大分子）负载，达到了良好的负载（2.42%相对于理论4.00% w/w），并且释放时间延长超过60天。GE11-PLGA/PEG-PLGA共混纳米颗粒在4℃生理盐水溶液中表现出良好的体外稳定性，在pH 7.4或pH 5.0缓冲液中表现出24 h的体外稳定性，为潜在的储存和给药条件提供了指示。此外，利用荧光单粒子跟踪（fSPT）对人血浆中的离体稳定性进行了研究，评估了良好的GE11-PLGA/PEG-PLGA纳米颗粒在1和4小时后的尺寸稳定性。由于聚合物成分的多功能性和纳米颗粒在药物掺入和释放方面的相对可调特性，GE11-PLGAJPEG-PLGA混合NPs可以被认为是非常有前途的智能纳米颗粒平台，用于通过肠外给药治疗以EGFR过表达为特征的疾病。(C) 2016 Elsevier B.V.版权所有
Active drug targeting and controlled release of hydrophilic macromolecular drugs represent crucial points in designing efficient polymeric drug delivery nanoplatforms. In the present work EGFR-targeted polylactide-co-glycolide (PLGA) nanoparticles were made by a blend of two different PLGA-based polymers. The first, GE11-PLGA, in which PLGA was functionalized with GE11, a small peptide and EGFR allosteric ligand, able to give nanoparticles selective targeting features. The second polymer was a PEGylated PLGA (PEG-PLGA) aimed at improving nanoparticles hydrophilicity and stealth features. GE11 and GE11-PLGA were custom synthetized through a simple and inexpensive method. The nano precipitation technique was exploited for the preparation of polymeric nanoparticles composed by a 1:1 weight ratio between GE11-PLGA and PEG-PLGA, obtaining smart nanoplatforms with proper size for parenteral administration (143.9 +/- 5.0 nm). In vitro cellular uptake in EGFR-overexpressing cell line (A549) demonstrated an active internalization of GE11-functionalized nanoparticles. GE11-PLGA/PEG-PLGA blend nanoparticles were loaded with Myoglobin, a model hydrophilic macromolecule, reaching a good loading (2.42% respect to the theoretical 4.00% w/w) and a prolonged release over 60 days. GE11-PLGA/PEG-PLGA blend nanoparticles showed good in vitro stability for 30 days in physiological saline solution at 4 degrees C and for 24 h in pH 7.4 or pH 5.0 buffer at 37 degrees C respectively, giving indications about potential storage and administration conditions. Furthermore ex vivo stability study in human plasma using fluorescence Single Particle Tracking (fSPT) assessed good GE11-PLGA/PEG-PLGA nanoparticles dimensional stability after 1 and 4 h. Thanks to the versatility in polymeric composition and relative tunable nanoparticles features in terms of drug incorporation and release, GE11-PLGAJPEG-PLGA blend NPs can be considered highly promising as smart nanoparticulate platforms for the treatment of diseases characterized by EGFR overexpression by parenteral administration. (C) 2016 Elsevier B.V. All rights reserved.