Long-circulating polymeric nanoparticles bearing a combinatorial coating of PEG and water-soluble chitosan
Long-circulating polymeric nanoparticles bearing a combinatorial coating of PEG and water-soluble chitosan
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DOI：
10.1016/j.biomaterials.2008.12.070
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发表时间：
2009-04-01
期刊：
影响因子：
14
通讯作者：
Xu, Feng
中科院分区：
文献类型：
--
作者：
Sheng, Yan;Liu, Changsheng;Xu, Feng
聚合物纳米颗粒（NPs）作为有效药物递送囊泡的发展中的主要障碍是从血液中的快速清除。为了实现血液循环的显着延长，一个组合的设计，共价连接聚乙二醇（PEG）的聚乳酸（PLA）和物理吸附的水溶性壳聚糖（WSC）的颗粒表面，已开发的PLA纳米粒子的表面改性。研究了阳离子部分脱乙酰甲壳素（PDC）和阴离子N-羧基丙酰壳聚糖钠（CPCTS）两种水溶性壳聚糖。通过改进的w/o/w技术制备在100-200 nm尺寸范围内配制的所有NP并进行物理化学表征。对6-香豆素标记的纳米粒进行了小鼠腹腔巨噬细胞（MPM）的体外吞噬作用、小鼠静脉给药后的体内血液清除率和生物分布评价。WSC的存在。无论是单独使用还是与PEG一起使用，都极大地改善了纳米颗粒的表面亲水性以及悬浮稳定性。它们的表面电荷受到WSC涂层的极大影响，对于PEG/PDC NP接近中性，并且在PEG/CPCTS NP的情况下为高度负性。与单独用PEG或WSC处理的NP相比，PEG和WSC的协同作用强烈抑制巨噬细胞摄取并延长循环半衰期（t（1/2）），同时减少肝脏隔离。特别地，PEG/PDC NP在体外和体内表现出最显著的结果。PEG/PDC纳米颗粒和PEG/CPCTS纳米颗粒的t（1/2）分别为63.5 h和7.1 h，远长于对照PEG/PVA纳米颗粒的t（1/2）（1.1 h）。需要评估更多的WSC材料，但目前的数据表明，PEG和PDC的组合涂层极大地改善了NP的体循环，代表了长循环药物递送载体开发的重要一步。(C)2008爱思唯尔有限公司保留所有权利。
A major obstacle in the development of polymeric nanoparticles (NPs) as effective drug delivery vesicles is the rapid clearance from blood. In order to realize a significant prolongation in blood circulation, a combinatorial design, covalent attachment of polyethylene glycol (PEG) to polylactic acid (PLA) and physical adsorption of water-soluble chitosan (WSC) to particle surface, has been developed for surface modification of PLA NPs. Two types of WSC, cationic partially deacetylated chitin (PDC) and anionic N-carboxy propionyl chitosan sodium (CPCTS) were investigated. All the NPs formulated in the size range of 100-200 nm were prepared by a modified w/o/w technique and physicochemically characterized. In vitro phagocytosis by mouse peritoneal macrophage (MPM), in vivo blood clearance and biodistribution following intravenous administration in mice, of these NPs labeled with 6-coumarin, were evaluated. The presence of WSC. whether alone or with PEG, highly improved the surface hydrophilicity as well as suspension stability of NPs. Their surface charge was greatly affected by the WSC coating, being close to neutrality for PEG/PDC NPs and highly negative in the case of PEG/CPCTS NPs. In comparison to NPs treated with PEG or WSC alone, the synergistic action of PEG and WSC strongly inhibited the macrophage uptake and extended the circulation half-life (t(1/2)) with concomitant reduced liver sequestration. Particularly, PEG/PDC NPs showed the most striking result with regard to their performance in vitro and in vivo. Calculated t(1/2) of PEG/PDC NPs and PEG/CPCTS NPs was 63.5 h and 7.1 h, respectively, much longer than that of control PEG/PVA NPs (1.1 h). More WSC materials need to be evaluated, but the present data suggest that, a combinatorial coating of PEG and PDC greatly prolongs the systemic circulation of NPs and represents a significant step in the development of long-circulating drug delivery carriers. (C) 2008 Elsevier Ltd. All rights reserved.