A Nano-in-Nano Vector: Merging the Best of Polymeric Nanoparticles and Drug Nanocrystals
A Nano-in-Nano Vector: Merging the Best of Polymeric Nanoparticles and Drug Nanocrystals
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DOI：
10.1002/adfm.201604508
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发表时间：
2017-03-03
影响因子：
19
通讯作者：
Santos, Helder A.
中科院分区：
文献类型：
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作者：
Liu, Dongfei;Bernuz, Cristina Rodriguez;Santos, Helder A.
一种先进的方法可以制备窄尺寸分布的纳米材料，具有超高的治疗剂质量分数、优异的胶体稳定性、最小的偏离靶标效应以及精确控制的药物释放曲线。在这里，我们成功地制备了由药物(索拉非尼，SFN或伊曲康唑，ICZ)纳米晶核和聚合物(叶酸结合精胺功能化缩醛葡聚糖，ADS-FA)按1：1的比例组成的最佳纳米载体(HSFN@ADS-FA或ICZ@ADS-FA)。借助于计算流体力学，计算了纳米矢量前驱体在微流体域的浓度场和速度场，以及溶剂和非溶剂的混合时间。所获得的纳米载体继承了聚合物纳米粒和药物纳米晶的优点，表现出超高的载药量、生物降解性、pH响应快、在血清中的稳定性高、易于表面功能化。此外，载药纳米HSFN@ADS-FA的半最大抑制浓度比常规载药纳米载体(LSFN@ADS-FA)低约54倍。总体而言，这种纳米载体融合了聚合物纳米颗粒和药物纳米晶体的优点。
An advanced approach that can prepare narrowly size distributed nanomaterials with ultrahigh mass fraction of therapeutics, superior colloidal stability, minimal off-target effects, as well as precisely controlled drug-release profiles, is strongly desirable. Here, an optimal nano-in-nano vector, consisting of a drug (sorafenib, SFN, or itraconazole, ICZ) nanocrystal core and a polymer (folic acid conjugated spermine-functionalized acetalated dextran, ADS-FA) shell on a 1:1 ratio (HSFN@ADS-FA or ICZ@ADS-FA) is successfully fabricated. With the help of computational fluid dynamics, the concentration and velocity field are computed in the microfluidic domain, as well as the mixing time between the solvent and nonsolvent for nanovector precursors. The favorable features of both polymer nanoparticles and drug nanocrystals are inherited by the obtained nano-in-nano vector, showing ultrahigh drug-loading degree, biodegradability, pH-responsive fast dissolution, high stability in serum, and ease of surface functionalization. Furthermore, the half-maximal inhibitory concentration value of the nano-in-nano HSFN@ADS-FA is approximate to 54 times lower than the conventional nanovector (LSFN@ADS-FA) with a low drug-loading degree. Overall, this nano-in-nano vector merges the best of polymeric nanoparticles and drug nanocrystals.