Preparation of chitosan/tripolyphosphate nanoparticles with highly tunable size and low polydispersity
Preparation of chitosan/tripolyphosphate nanoparticles with highly tunable size and low polydispersity
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DOI：
10.1016/j.colsurfb.2017.05.055
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发表时间：
2017-09-01
影响因子：
5.8
通讯作者：
Lapitsky, Yakov
中科院分区：
文献类型：
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作者：
Sawtarie, Nader;Cai, Yuhang;Lapitsky, Yakov
壳聚糖与三聚磷酸盐（TPP）离子凝胶化制备的纳米粒作为药物和基因载体已被广泛研究。尽管许多这些工作集中于制备具有窄尺寸分布的颗粒，但是通过这些方法生产的单分散颗粒限于窄尺寸范围（其中平均颗粒尺寸的变化不超过两倍）。在这里，我们展示了如何，通过调整在母体壳聚糖和TPP溶液中的NaCl浓度，可以制备z-平均直径在大约100和900 nm之间的低多分散性颗粒。此外，我们探索这些颗粒的大小如何取决于TPP混合到壳聚糖溶液中的方法，具体比较：（1）单次混合;（2）逐滴添加;和（3）稀释技术，其中壳聚糖和TPP在高（凝胶抑制）离子强度下共溶解，然后稀释至较低的离子强度以引发凝胶化。尽管对于所有三种混合方法，粒度随NaCl浓度呈S形增加，但稀释方法提供最均匀/逐渐的粒度增加，即，它提供了最精确的控制。还研究了混合物组成和混合程序对颗粒产率的影响。这些揭示了颗粒产率随着壳聚糖/TPP浓度增加，随着NaCl浓度降低，并且随着混合方案仅微弱变化;因此，在升高的NaCl浓度下，增加壳聚糖和TPP浓度以确保高颗粒产率可能是有益的。最后，盐辅助尺寸控制策略（及其解决方案）的可能陷阱进行了讨论。总之，这些发现提供了一种简单可靠的方法，广泛调整壳聚糖/TPP粒径，同时保持窄的尺寸分布。(C)2017爱思唯尔B.V.保留所有权利。
Nanoparticles prepared through the ionotropic gelation of chitosan with tripolyphosphate (TPP) have been extensively studied as vehicles for drug and gene delivery. Though a number of these works have focused on preparing particles with narrow size distributions, the monodisperse particles produced by these methods have been limited to narrow size ranges (where the average particle size was not varied by more than twofold). Here we show how, by tuning the NaCl concentration in the parent chitosan and TPP solutions, low-polydispersity particles with z-average diameters ranging between roughly 100 and 900 nm can be prepared. Further, we explore how the size of these particles depends on the method by which the TPP is mixed into the chitosan solution, specifically comparing: (1) single-shot mixing; (2) dropwise addition; and (3) a dilution technique, where chitosan and TPP are codissolved at a high (gelation-inhibiting) ionic strength and then diluted to lower ionic strengths to trigger gelation. Though the particle size increases sigmoidally with the NaCl concentration for all three mixing methods, the dilution method delivers the most uniform/gradual size increase i.e., it provides the most precise control. Also investigated are the effects of mixture composition and mixing procedure on the particle yield. These reveal the particle yield to increase with the chitosan/TPP concentration, decrease with the NaCl concentration, and vary only weakly with the mixing protocol; thus, at elevated NaCl concentrations, it may be beneficial to increase chitosan and TPP concentrations to ensure high particle yields. Finally, possible pitfalls of the salt-assisted size control strategy (and their solutions) are discussed. Taken together, these findings provide a simple and reliable method for extensively tuning chitosan/TPP particle size while maintaining narrow size distributions. (C) 2017 Elsevier B.V. All rights reserved.