The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups
The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups
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DOI：
10.1016/j.biomaterials.2003.09.024
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发表时间：
2004-05-01
期刊：
影响因子：
14
通讯作者：
Hennink, WE
中科院分区：
文献类型：
--
作者：
Neradovic, D;Soga, O;Hennink, WE
聚乙二醇（PEG）为亲水性嵌段，n -异丙基丙烯酰胺（PNIPAAm）或聚（NIPAAm-co-N-（2-羟丙基）二乙基丙烯酰胺-dilactate）（聚（NIPAAm-co-HPMAm-dilactate））为热敏嵌段的嵌段共聚物，能够在热敏嵌段云点（CP）上方的水中自组装成纳米颗粒。采用动态光散射技术研究了制备工艺和配方参数对纳米颗粒尺寸的影响。PNIPAAm-b-PEG 2000聚合物不适合形成小而稳定的颗粒。PEG 5000和10000嵌段共聚物在高于热敏嵌段CP的温度下在水溶液中形成相对小而稳定的颗粒。随着热敏块体分子量的增加、聚合物浓度的降低以及用水代替磷酸盐缓冲盐水作为溶剂，热敏块体的尺寸减小。挤出法和超声波法是降低聚合物纳米颗粒尺寸的低效方法。聚合物溶液的加热速率是决定纳米颗粒尺寸的主要因素。当聚合物水溶液通过CP缓慢加热时，形成相当大的颗粒（大于或等于200 nm）。无论聚合物的组成如何，当将低于CP的小体积聚合物水溶液加入到大体积的加热水中时，形成了尺寸分布狭窄的小纳米颗粒（50-70nm）。通过这种方式，热敏嵌段共聚物迅速通过CP（“热冲击”程序），产生小而稳定的纳米颗粒。(C) 2003 Elsevier Ltd.版权所有。
Block copolymers of poly(ethylene glycol) (PEG) as a hydrophilic block and N-isopropylacrylamide (PNIPAAm) or poly (NIPAAm-co-N-(2-hydroxypropyl) tuethacrylamide-dilactate) (poly(NIPAAm-co-HPMAm-dilactate)) as a thermosensitive block, are able to self-assemble in water into nanoparticles above the Cloud point (CP) of the thermosensitive block. The influence of processing and the formulation parameters on the size of the nanoparticles was studied using dynamic light scattering. PNIPAAm-b-PEG 2000 polymers were not suitable for the formation of small and stable particles. Block copolymers with PEG 5000 and 10 000 formed relatively small and stable particles in aqueous solutions at temperatures above the CP of the thermosensitive block. Their size decreased with increasing molecular weight of the thermosensitive block, decreasing polymer concentration and using water instead of phosphate buffered saline as solvent. Extrusion and ultrasonication were inefficient methods to size down the polymeric nanoparticles. The heating rate of the polymer solutions was a dominant factor for the size of the nanoparticles. When an aqueous polymer solution was slowly heated through the CP, rather large particles (greater than or equal to-200 nm) were formed. Regardless the polymer composition, small nanoparticles (50-70nm) with a narrow size distribution were formed, when a small volume of an aqueous polymer solution below the CP was added to a large Volume of heated water. In this way the thermosensitive block copolymers rapidly pass their CP ('heat shock' procedure), resulting in small and stable nanoparticles. (C) 2003 Elsevier Ltd. All rights reserved.