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.