Colaço Mariana, Roquito Tiago, Costa João Panão, Cruz Maria Teresa, Borges Olga
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.
Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
Pharmaceutics. 2023 Feb 13;15(2):623. doi: 10.3390/pharmaceutics15020623.
Curcumin is known for its multiple health benefits, largely due to its antioxidant and anti-inflammatory properties. It has been extensively studied as a therapeutic agent, however, it does not have good clinical efficacy due to its poor water solubility and bioavailability. Despite accepting the encapsulation of this compound in polymeric particles as one of the most promising strategies to increase its therapeutic value, these nanoparticles have fallen short of expectations due to a lack of assessment of their possible adverse effects on the immune system. Therefore, in this work, we report on a new method to encapsulate curcumin into glucan nanoparticles and their effects on cells of the immune system were evaluated. Two different-sized curcumin-loaded glucan NPs (GluCur 100 and GluCur 380) were produced, each with an encapsulation efficiency close to 100%, and were characterized regarding their size distribution, surface properties, and morphology. The results revealed the greatest hemolytic effect and cytotoxicity for the smallest particles (100 nm) tested in human PBMCs and RAW 264.7 cells. Although GluCur 380 NPs showed a weaker ROS production, they were able to inhibit the production of NO by macrophages. Furthermore, we found that the coagulation time was not affected by both sized-particles as well as platelet function. Additionally, both nanoparticles induced lymphocyte proliferation and TNF-α secretion by Mo-DCs. In conclusion, this report emphasizes the importance of the immunotoxicity assessment and how this is dependent on the intrinsic properties of nanomaterials, hopefully contributing to increasing the safety of nanomedicines.
姜黄素因其多种健康益处而闻名，这主要归功于其抗氧化和抗炎特性。它作为一种治疗剂已被广泛研究，然而，由于其水溶性和生物利用度差，其临床疗效并不理想。尽管将这种化合物封装在聚合物颗粒中被认为是提高其治疗价值的最有前景的策略之一，但由于缺乏对其对免疫系统可能产生的不良反应的评估，这些纳米颗粒并未达到预期效果。因此，在这项工作中，我们报告了一种将姜黄素封装到葡聚糖纳米颗粒中的新方法，并评估了它们对免疫系统细胞的影响。制备了两种不同尺寸的负载姜黄素的葡聚糖纳米颗粒（GluCur 100和GluCur 380），每种的包封效率都接近100%，并对其尺寸分布、表面性质和形态进行了表征。结果显示，在人外周血单核细胞（PBMCs）和RAW 264.7细胞中测试的最小颗粒（100 nm）具有最大的溶血作用和细胞毒性。虽然GluCur 380纳米颗粒显示出较弱的活性氧（ROS）产生，但它们能够抑制巨噬细胞产生一氧化氮（NO）。此外，我们发现凝血时间不受这两种尺寸颗粒以及血小板功能的影响。此外，两种纳米颗粒均能诱导单核细胞来源的树突状细胞（Mo-DCs）的淋巴细胞增殖和肿瘤坏死因子-α（TNF-α）分泌。总之，本报告强调了免疫毒性评估的重要性以及它如何依赖于纳米材料的固有特性，有望有助于提高纳米药物的安全性。
