Janes K A, Fresneau M P, Marazuela A, Fabra A, Alonso M J
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, The University of Santiago de Compostela, 15706, Santiago de Compostela, Spain.
J Control Release. 2001 Jun 15;73(2-3):255-67. doi: 10.1016/s0168-3659(01)00294-2.
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.
本文旨在评估壳聚糖纳米颗粒作为蒽环类药物阿霉素（DOX）载体的潜力。面临的挑战是将一种阳离子亲水分子包裹在由带正电荷的多糖壳聚糖通过离子凝胶化形成的纳米颗粒中。为实现这一目标，我们尝试通过将DOX与聚阴离子硫酸葡聚糖络合来掩盖其正电荷。这种修饰使DOX的包封效率相对于对照组提高了一倍，并实现了高达4.0 wt.%的DOX实际负载量。另外，我们研究了在颗粒形成之前壳聚糖与DOX形成络合物的可能性。尽管络合效率较低，但在纳米颗粒形成后未观察到络合物的解离。对体外释放药物的荧光分析显示出一个初始释放阶段，其强度取决于缔合模式，随后是非常缓慢的释放。对负载DOX的纳米颗粒在细胞培养中的活性评估表明，含有硫酸葡聚糖的纳米颗粒相对于游离DOX能够维持细胞生长抑制活性，而在纳米颗粒形成之前与壳聚糖络合的DOX活性略有下降。此外，共聚焦研究表明，DOX未在细胞培养基中释放，而是进入细胞并与纳米颗粒保持缔合。总之，这些初步研究表明壳聚糖纳米颗粒能够包裹碱性药物DOX并以其活性形式将其递送至细胞中的可行性。
