Analysis of chitosan/tripolyphosphate micro- and nanogel yields is key to understanding their protein uptake performance
Analysis of chitosan/tripolyphosphate micro- and nanogel yields is key to understanding their protein uptake performance
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DOI：
10.1016/j.jcis.2017.01.066
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发表时间：
2017-05-15
影响因子：
9.9
通讯作者：
Lapitsky, Yakov
中科院分区：
文献类型：
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作者：
Cai, Yuhang;Lapitsky, Yakov
壳聚糖/三聚磷酸盐(TPP)微凝胶和纳米凝胶作为蛋白质、药物和疫苗输送的载体被广泛探索。然而，除了更强的蛋白质/颗粒结合增强了蛋白质对这些颗粒的吸收这一共识外，控制它们吸收性能的因素，如壳聚糖、TPP和蛋白质浓度的差异，仍然知之甚少。在这里，我们表明，所报道的蛋白质摄取的缔合效率(AE值)的许多差异可能反映了颗粒产率(X-Agg)的大部分被忽略的变异性，颗粒产率(X-Agg)是添加的壳聚糖自组装成颗粒的部分，并且(像AE)随着壳聚糖、TPP和蛋白质浓度的不同而变化。首次系统地研究了影响X-AgG的因素。然后显示AE几乎与X-Agg成线性关系(X-Agg随TPP和蛋白质与壳聚糖的比例增加而增加)，直到所有壳聚糖聚集成颗粒。值得注意的是，在不同的TPP和蛋白质浓度下收集的数据崩溃到与每种蛋白质类型的X-Agg曲线成比例的单个AE上。对蛋白质/颗粒结合的进一步分析揭示了这种与X-Agg结合的AE的增加，以反映：(1)颗粒内结合部位的增加；以及(2)可溶(非颗粒)壳聚糖分子的减少，这些分子形成可溶的蛋白质/壳聚糖复合体，并与壳聚糖/TPP颗粒竞争未结合的蛋白质。这些发现强调了仔细分析配方参数对壳聚糖/TPP颗粒产率的影响的必要性，并可能推广到其他离子交联型胶体药物载体。(C)2017 Elsevier Inc.保留所有权利。
Chitosan/tripolyphosphate (TPP) micro- and nanogels are widely explored as vehicles for protein drug and vaccine delivery. Yet, aside from the consensus that protein uptake into these particles is enhanced by stronger protein/particle binding, factors that control their uptake performance, such as differences in the chitosan, TPP and protein concentrations, remain poorly understood. Here, we show that many of the differences in the reported association efficiencies (AE-values) for protein uptake likely reflect the largely ignored variability in the particle yield (X-Agg), which is the fraction of the added chitosan that self assembles into particles and (like the AE) varies with the chitosan, TPP and protein concentrations. Factors affecting X-Agg are first systematically explored. The AE is then shown to scale almost linearly with the X-Agg (which increases with the TPP and protein-to-chitosan ratios) until all chitosan aggregates into particles. Remarkably, the data collected at variable TPP and protein concentrations collapses onto a single AE proportional to X-Agg curve for each protein type. Further analysis of protein/particle binding reveals this rise in AE with X-Agg to reflect: (1) an increase in binding sites within the particles; and (2) a decrease in soluble (non-particulate) chitosan molecules, which form soluble protein/chitosan complexes and compete with the chitosan/TPP particles for the unassociated protein. These findings highlight the need to carefully analyze the effects of formulation parameters on chitosan/TPP particle yields and can likely be extended to other ionically crosslinked colloidal drug carriers. (C) 2017 Elsevier Inc. All rights reserved.