Flash nanoprecipitation: prediction and enhancement of particle stability via drug structure.
Flash nanoprecipitation: prediction and enhancement of particle stability via drug structure.
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DOI：
10.1021/mp500025e
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发表时间：
2014-03-03
影响因子：
4.9
通讯作者：
Zhu Z
中科院分区：
文献类型：
--
作者：
Zhu Z
闪光纳米沉淀法可以在∼100 nm处生成疏水性药物纳米颗粒，并且载药量(例如40wt%)比传统纳米载体(例如20wt%)高得多。本文研究了药物分子对FNP法制备的纳米粒稳定性的影响，证明了将药物化合物(如紫杉醇)与可切割的疏水部分有机硅酸盐(如三乙氧基硅酸盐)化学键合可提高纳米粒的尺寸稳定性。非离子两亲嵌段共聚物聚(乳酸-乙醇酸)-嵌段-聚乙二醇(PLGA-b-PEG)被用作提供空间稳定的模型表面活性剂。实验表明，药物在水介质中的溶解度越低，颗粒在Ostwald熟化过程中越稳定，这与LSW理论的预测是一致的。初始颗粒大小分布非常窄，对Ostwald熟化没有意义。为了将颗粒稳定性与疏水性联系起来，本研究将疏水性指标正辛醇/水分配系数(LogP)引入FNP技术。各种药物及其类似物的比较表明，药物的对数P是一个比溶解度参数(δ)更好的疏水性指标，并且与颗粒稳定性有很好的相关性。经验上，使用ACDLogP&>∼12，纳米粒具有良好的稳定性；使用∼2<；ACDLogP<；∼9，纳米粒表现出快速的Ostwald熟化和颗粒间重结晶；使用ACDLogP<；∼2，药物很可能难以形成纳米粒。这一规则创建了一种快速预测随机选择的药物结构的颗粒稳定性的方法，并有助于实现快速的临床前药物筛选。
Flash nanoprecipitation (FNP) can generate hydrophobic drug nanoparticles in ∼100 nm with a much higher drug loading (e.g., > 40 wt %) than traditional nanocarriers (e.g., < 20 wt %). This paper studies the effects of drug molecules on nanoparticle stability made via FNP and demonstrates that chemically bonding a drug compound (e.g., paclitaxel) with a cleavable hydrophobic moiety of organosilicate (e.g., triethoxysilicate) is able to enhance the particle size stability. A nonionic amphiphilic diblock copolymer, poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG), is used as a model surfactant to provide steric stabilization. The experiments here show that the lower the drug solubility in the aqueous medium, the more stable the particles in terms of Ostwald ripening, which are consistent with the prediction by the LSW theory. The initial particle size distribution is sufficiently narrow and of insignificance to Ostwald ripening. To correlate the particle stability with hydrophobicity, this study introduces the n-octanol/water partition coefficient (LogP), a hydrophobicity indication, into the FNP technique. A comparison of various drugs and their analogues shows that LogP of a drug is a better hydrophobicity indication than the solubility parameter (δ) and correlates well with the particle stability. Empirically, with ACDLogP > ∼12, nanoparticles have good stability; with ∼2 < ACDLogP < ∼9, nanoparticles show fast Ostwald ripening and interparticle recrystallization; with ACDLogP < ∼2, the drug is very likely difficult to form nanoparticles. This rule creates a quick way to predict particle stability for a randomly selected drug structure and helps to enable a fast preclinical drug screen.
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影响因子：
4.7
作者：
Liu, Ying;Cheng, Chungyin;Fox, Rodney O.
通讯作者：
Fox, Rodney O.
DOI：
10.1021/je900376r
发表时间：
2010-01-01
期刊：
JOURNAL OF CHEMICAL AND ENGINEERING DATA
影响因子：
--
作者：
Ali, Hany S. M.;York, Peter;Jouyban, Abolghasem
通讯作者：
Jouyban, Abolghasem
影响因子：
9.9
作者：
Choi, P;Kavassalis, T;Rudin, A
通讯作者：
Rudin, A
影响因子：
--
作者：
Jakes, J
通讯作者：
Jakes, J
影响因子：
3.7
作者：
Johnson, BK;Prud'homme, RK
通讯作者：
Prud'homme, RK