Flash nanoprecipitation: particle structure and stability.
Flash nanoprecipitation: particle structure and stability.
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DOI：
10.1021/mp400337f
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发表时间：
2013-11-04
影响因子：
4.9
通讯作者：
Macosko CW
中科院分区：
文献类型：
--
作者：
Pustulka KM;Wohl AR;Lee HS;Michel AR;Han J;Hoye TR;McCormick AV;Panyam J;Macosko CW
闪速纳米沉淀（FNP）是一种通过快速混合，在纳米级聚合物稳定的运载工具中稳定不溶性低分子量化合物的过程。聚合物组分通常为两亲性二嵌段共聚物（bcp）。为了充分开发FNP的潜力，必须了解影响颗粒结构、大小和稳定性的因素。研究表明，聚合物类型、小分子的疏水性和结晶度以及小分子的负载水平都会影响颗粒的大小和稳定性。在我们研究的四种嵌段共聚物（BCP）中，聚（乙二醇）-b-聚（乳酸-羟基乙酸）（PEG-b-PLGA）由于其产生稳定纳米颗粒的能力、生物相容性和可降解性，最适合于潜在的药物递送应用。我们发现在5到15kDa范围内使用PLGA块尺寸时，粒径差异很小。疏水小分子的选择很重要，因为计算出的水-辛醇分配系数（clogP）低于6的分子会产生不稳定的颗粒，并经历快速的奥斯特瓦尔德成熟。研究探测纳米颗粒的内部结构也进行了。差示扫描量热法（DSC）、低温透射电镜（cro - tem）和1H-NMR实验的分析支持了核-壳-电晕三层纳米颗粒结构。
Flash nanoprecipitation (FNP) is a process that, through rapid mixing, stabilizes an insoluble low molecular weight compound in a nano-sized, polymer-stabilized delivery vehicle. The polymeric components are typically amphiphilic diblock copolymers (BCPs). In order to fully exploit the potential of FNP, factors affecting particle structure, size, and stability must be understood. Here we show that polymer type, hydrophobicity and crystallinity of the small molecule, and small molecule loading levels all affect particle size and stability. Of the four block copolymers (BCP) that we have studied here, poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-b-PLGA) was most suitable for potential drug delivery applications due to its ability to give rise to stable nanoparticles, its biocompatibility, and its degradability. We found little difference in particle size when using PLGA block sizes over the range of 5 to 15kDa. The choice of hydrophobic small molecule was important, as molecules with a calculated water-octanol partition coefficient (clogP) below 6 gave rise to particles that were unstable and underwent rapid Ostwald ripening. Studies probing the internal structure of nanoparticles were also performed. Analysis of differential scanning calorimetry (DSC), cryogenic transmission electron microscopy (cryo-TEM), and 1H-NMR experiments support a three-layer core-shell-corona nanoparticle structure.
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