Lazaridou Maria, Christodoulou Evi, Nerantzaki Maria, Kostoglou Margaritis, Lambropoulou Dimitra A, Katsarou Angeliki, Pantopoulos Kostas, Bikiaris Dimitrios N
Laboratory of Polymer Chemistry and Technology, Chemistry Department, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Laboratory of General and Inorganic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki, Greece.
Pharmaceutics. 2020 Mar 7;12(3):238. doi: 10.3390/pharmaceutics12030238.
The objective of this study was to develop chitosan (CS) nanoparticles (NPs) loaded with deferoxamine mesylate (DFO) for slow release of this iron-chelating drug. Drug nanoencapsulation was performed via ionic gelation of chitosan using sodium tripolyphosphate (TPP) as cross-linker. Nanoparticles with a size ranging between 150 and 400 nm were prepared for neat CS/TPP with a 2/1 molar ratio while their yield was directly dependent on the applied stirring rate during the preparation process. DFO at different content (20, 45 and 75 wt %) was encapsulated into these nanoparticles. We found that drug loading correlates with increasing DFO content while the entrapment efficiency has an opposite behavior due to the high solubility of DFO. Hydrogen-bonding between amino and hydroxyl groups of DFO with reactive groups of CS were detected using FT-IR spectroscopy while X-ray diffraction revealed that DFO was entrapped in amorphous form in the CS nanoparticles. DFO release is directly dependent on the content of loaded drug, while model analysis revealed that the release mechanism of DFO for the CS/TPP nanoparticles is by diffusion. Treatment of murine RAW 264.7 macrophages with nanoencapsulated DFO promoted an increased expression of transferrin receptor 1 (TfR1) mRNA, a typical homeostatic response to iron deficiency. These data provide preliminary evidence for release of pharmacologically active DFO from the chitosan nanoparticles.
本研究的目的是开发负载甲磺酸去铁胺（DFO）的壳聚糖（CS）纳米颗粒（NPs），用于这种铁螯合药物的缓释。通过使用三聚磷酸钠（TPP）作为交联剂对壳聚糖进行离子凝胶化来实现药物纳米包封。制备了摩尔比为2/1的纯CS/TPP纳米颗粒，其尺寸在150至400nm之间，而其产率直接取决于制备过程中施加的搅拌速率。将不同含量（20、45和75wt%）的DFO包封到这些纳米颗粒中。我们发现载药量与DFO含量的增加相关，而由于DFO的高溶解度，包封效率呈现相反的趋势。使用傅里叶变换红外光谱（FT-IR）检测了DFO的氨基和羟基与CS的反应基团之间的氢键，而X射线衍射表明DFO以无定形形式包封在CS纳米颗粒中。DFO的释放直接取决于载药量，而模型分析表明CS/TPP纳米颗粒中DFO的释放机制是扩散。用纳米包封的DFO处理小鼠RAW 264.7巨噬细胞可促进转铁蛋白受体1（TfR1）mRNA表达增加，这是对铁缺乏的典型稳态反应。这些数据为壳聚糖纳米颗粒释放具有药理活性的DFO提供了初步证据。
