Chitosan nanoparticles as delivery systems for doxorubicin
Chitosan nanoparticles as delivery systems for doxorubicin
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DOI：
10.1016/s0168-3659(01)00294-2
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发表时间：
2001-06-15
影响因子：
10.8
通讯作者：
Alonso, MJ
中科院分区：
文献类型：
--
作者：
Janes, KA;Fresneau, MP;Alonso, MJ
本文的目的是评估壳聚糖纳米粒作为蒽环类药物阿霉素（DOX）载体的潜力。挑战是将阳离子亲水性分子捕获到由带正电荷的多糖壳聚糖的离子凝胶化形成的纳米颗粒中。为了实现这一目标，我们试图通过将DOX与聚阴离子硫酸葡聚糖络合来掩蔽DOX的正电荷。这种修饰使DOX包封效率相对于对照加倍，并使真实的负载量达到4.0重量% DOX。另外，我们研究了在形成颗粒之前在壳聚糖和DOX之间形成复合物的可能性。尽管复合效率较低，但在形成纳米颗粒时没有观察到复合物的解离。体外释放的药物的荧光分析显示了初始释放阶段，其强度取决于缔合模式，随后是非常缓慢的释放。在细胞培养物中对载有DOX的纳米颗粒的活性的评价表明，相对于游离DOX，含有硫酸葡聚糖的纳米颗粒能够保持细胞抑制活性，而在纳米颗粒形成之前与壳聚糖复合的DOX显示出轻微降低的活性。另外。共聚焦研究显示DOX不在细胞培养基中释放，而是进入细胞，同时保持与纳米颗粒结合。总之，这些初步研究表明，壳聚糖纳米颗粒包埋基础药物DOX并以其活性形式将其递送到细胞中的可行性，（C）2001 Elsevier Science B.V.保留所有权利。
The aim of this paper was to evaluate the potential of chitosan nanoparticles as carriers for the anthracycline drug, doxorubicin (DOX). The challenge was to entrap a cationic, hydrophilic molecule into nanoparticles formed by ionic gelation of the positively charged polysaccharide chitosan. To achieve this objective, we attempted to mask the positive charge of DOX by complexing it with the polyanion, dextran sulfate. This modification doubled DOX encapsulation efficiency relative to controls and enabled real loadings up to 4.0 wt.% DOX. Separately, we investigated the possibility of forming a complex between chitosan and DOX prior to the formation of the particles. Despite the low complexation efficiency, no dissociation of the complex was observed upon formation of the nanoparticles. Fluorimetric analysis of the drug released in vitro showed an initial release phase, the intensity of which was dependent on the association mode, followed by a very slow release, The evaluation of the activity of DOX-loaded nanoparticles in cell cultures indicated that those containing dextran sulfate were able to maintain cytostatic activity relative to free DOX, while DOX complexed to chitosan before nanoparticle formation showed slightly decreased activity. Additionally. confocal studies showed that DOX was not released in the cell culture medium but entered the cells while remaining associated to the nanoparticles. In conclusion, these preliminary studies showed the feasibility of chitosan nanoparticles to entrap the basic drug DOX and to deliver it into the cells in its active form, (C) 2001 Elsevier Science B.V. All rights reserved.