PLGA-LEC/F127 hybrid nanoparticles loaded with curcumin and their modulatory effect on monocytes

<b>Aim:</b> To investigate the effect of surfactant type on curcumin-loaded (CUR) PLGA nanoparticles (NPs) to modulate monocyte functions. <b>Materials &amp; methods</b>: The nanoprecipitation method was used, and PLGA NPs were designed using Pluronic F127 (F127) and/or lecithin (LEC) as surfactants. <b>Results:</b> The Z-average of the NPs was &lt;200 nm, they had a spherical shape, Derjaguin–Muller–Toporov modulus &gt;0.128 MPa, they were stable during storage at 4°C, ζ-potential ∼-40 mV, polydispersity index &lt;0.26 and % EE of CUR &gt;94%. PLGA-LEC/F127 NPs showed favorable physicochemical and nanomechanical properties. These NPs were bound and internalized mainly by monocytes, suppressed monocyte-induced reactive oxygen species production, and decreased the ability of monocytes to modulate T-cell proliferation. <b>Conclusion:</b> These results demonstrate the potential of these NPs for targeted therapy. This study explores how different surfactants affect curcumin-loaded PLGA nanoparticles, a biodegradable polymer. The nanoparticles were designed using Pluronic F127 and/or lecithin as surfactants. They are less than 200 nm and spherical. They are stable when stored at 4 °C, with a surface charge of about -40 mV, and can encapsulate more than 94% of curcumin. The results of this study are promising, showing that PLGA nanoparticles using a mixture of lecithin and Pluronic F127 as surfactants have favorable properties toward monocyte adhesion. They are primarily taken up by monocytes, a type of white blood cell, and demonstrate a remarkable ability to reduce the production of reactive oxygen species, which can cause cell damage, as well as the ability of monocytes to stimulate the proliferation of T cells. This underscores the potential of these nanoparticles in targeted therapy, particularly in diseases where monocytes play a pivotal role, such as chronic inflammatory conditions. The consistency in size and ζ-potential across different nanoparticle formulations underscores the LEC/F127 mixture (70:30 wt/wt) potential in producing hybrid platforms with optimal physicochemical properties for biomedical applications. PLGA-LEC/F127 nanoparticles (NPs) showed higher hardness (Derjaguin–Muller–Toporov [DMT] = 0.406 MPa) compared with naked ones (DMT = 0.128 MPa) (Table 2), indicating that surfactant presence alters NPs elastic properties, increasing their hardness and cellular internalization. PLGA-LEC and PLGA-LEC/F127 NPs were preferentially bound/internalized by monocytes compared with neutrophils and lymphocytes. F127/LEC NPs did not significantly affect the mitochondrial membrane potential or plasma membrane integrity of peripheral blood mononuclear cells. Curcumin (CUR) was efficiently encapsulated within F127/LEC NPs. Free and encapsulated CUR reduced monocytes' ability to support autologous T-cell proliferation. Encapsulated CUR inhibited reactive oxygen species production by phorbol myristate acetate-stimulated monocytes. In some cases, encapsulating CUR in PLGA-LEC/F127 NPs enhances its inhibitory effects.

研究目的：探究表面活性剂种类对负载姜黄素（curcumin, CUR）的PLGA纳米粒（nanoparticles, NPs）调节单核细胞功能的影响。
材料与方法：采用纳米沉淀法，以泊洛沙姆F127（Pluronic F127, F127）和/或卵磷脂（lecithin, LEC）作为表面活性剂制备PLGA纳米粒。
结果：所制备纳米粒的Z均粒径小于200 nm，呈球形，Derjaguin-Muller-Toporov（DMT）模量大于0.128 MPa，4℃储存稳定性良好，ζ电位约为-40 mV，多分散指数小于0.26，姜黄素包封率（% EE）大于94%。其中PLGA-LEC/F127纳米粒展现出优异的理化与纳米力学性能。该类纳米粒主要可被单核细胞结合并内化，能够抑制单核细胞诱导的活性氧（reactive oxygen species, ROS）生成，同时削弱单核细胞调节T细胞增殖的能力。
结论：本研究结果证实了此类纳米粒用于靶向治疗的潜力。本研究探讨了不同表面活性剂对可生物降解聚合物PLGA负载姜黄素纳米粒的影响。实验采用泊洛沙姆F127和/或卵磷脂作为表面活性剂制备纳米粒，其粒径小于200 nm且呈球形，4℃储存稳定，表面电荷约为-40 mV，姜黄素包封率可超过94%。本研究结果令人振奋：以卵磷脂与泊洛沙姆F127混合物作为表面活性剂制备的PLGA纳米粒，具备适配单核细胞黏附的优良特性。该纳米粒主要被单核细胞（一类白细胞）摄取，可显著减少可引发细胞损伤的活性氧生成，同时抑制单核细胞诱导T细胞增殖的能力。这进一步凸显了此类纳米粒在靶向治疗中的应用潜力，尤其适用于单核细胞发挥关键作用的疾病，如慢性炎症性疾病。不同纳米粒制剂在粒径与ζ电位上的一致性，证实了70:30质量比的LEC/F127混合物在构建具备最优理化性能的杂化平台以用于生物医学应用方面的潜力。相较于裸纳米粒（DMT模量为0.128 MPa），PLGA-LEC/F127纳米粒的硬度更高（DMT模量为0.406 MPa）（表2），表明表面活性剂的存在可改变纳米粒的弹性特性，提升其硬度与细胞内化能力。相较于中性粒细胞与淋巴细胞，PLGA-LEC及PLGA-LEC/F127纳米粒更易被单核细胞结合/摄取。F127/LEC纳米粒对外周血单个核细胞的线粒体膜电位及质膜完整性无显著影响。姜黄素（CUR）可被高效包封于F127/LEC纳米粒中。游离与包封型姜黄素均可削弱单核细胞支持自体T细胞增殖的能力。包封型姜黄素可抑制佛波醇肉豆蔻酸乙酸酯刺激的单核细胞产生活性氧。在部分实验条件下，将姜黄素包封于PLGA-LEC/F127纳米粒中可增强其抑制效果。