Oxyresveratrol-Loaded PLGA Nanoparticles Inhibit Oxygen Free Radical Production by Human Monocytes: Role in Nanoparticle Biocompatibility

Abstract

Oxyresveratrol, a polyphenol extracted from the plant Artocarpus lakoocha Roxb, has been reported to be an antioxidant and an oxygen-free radical scavenger. We investigated whether oxyresveratrol affects the generation of superoxide anion (O2−) by human monocytes, which are powerful reactive oxygen species (ROS) producers. We found that oxyresveratrol inhibited the O2− production induced upon stimulation of monocytes with β-glucan, a well known fungal immune cell activator. We then investigated whether the inclusion of oxyresveratrol into nanoparticles could modulate its effects on O2− release. We synthesized poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and we assessed their effects on monocytes. We found that empty PLGA nanoparticles induced O2− production by resting monocytes and enhanced the formation of this radical in β-glucan-stimulated monocytes. Interestingly, the insertion of oxyresveratrol into PLGA nanoparticles significantly inhibited the O2− production elicited by unloaded nanoparticles in resting monocytes as well as the synergistic effect of nanoparticles and β-glucan. Our results indicate that oxyresveratrol is able to inhibit ROS production by activated monocytes, and its inclusion into PLGA nanoparticles mitigates the oxidative effects due to the interaction between these nanoparticles and resting monocytes. Moreover, oxyresveratrol can contrast the synergistic effects of nanoparticles with fungal agents that could be present in the patient tissues. Therefore, oxyresveratrol is a natural compound able to make PLGA nanoparticles more biocompatible.

mPEG-PLGA Nanoparticles Labelled with Loaded or Conjugated Rhodamine-B for Potential Nose-to-Brain Delivery

“…DNA damage stimulates ROS production in cell cultures [ 31 , 32 ]. ROS accumulation in cells treated with loaded- and grafted-PNPs at the highest concentrations could be attributed to a more effective internalization of the dye when delivered into the NPs [ 33 ].…”

Effects of Magnetic Nanoparticles on the Functional Activity of Human Monocytes and Dendritic Cells

“…The activation of the immune response by BMNPs was not entirely unexpected, because it is well known that immune cells undergo activation upon interaction with several nanoparticles [ 15 , 16 , 17 , 19 , 20 , 21 ], including some which are generally considered safe and biocompatible such as PLGA nanoparticles [ 18 , 22 ]. In particular, some magnetic iron oxide nanoparticles have been shown to increase ROS and pro-inflammatory cytokine release in THP 1 macrophages [ 62 ] and to enhance the levels of IL-2, interferon-γ and IL-10 in mice peripheral blood [ 63 ].…”

“…However, a crucial factor, not explored until now, is the potential immune response that these nanoparticles may trigger following application. In fact, it is well known that the administration of some nanoparticles to the patients causes adverse effects such as inflammation, as a consequence of the release of pro-inflammatory mediators and ROS by immune cells [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Therefore, it is essential to check the effect of BMNPs on immune cell activity to understand whether they can be safely injected into the patients for therapeutic purposes.…”

“…Finally, a nanoparticle unable to activate immune cells and, therefore, generally considered biocompatible, could instead enhance the pro-inflammatory effect of some microorganisms or their derivatives [ 18 , 43 , 44 , 45 ] through a cooperative event named “cell priming” [ 46 , 47 ]. This implies that, if this apparently harmless nanoparticle is administered to the patient in the presence of other agents such as pathogenic fungi, bacteria, or viruses, it might cause unwanted dangerous effects as it can induce a hyper-responsiveness of leukocytes to the above-mentioned agents.…”

Dual-Targeting Polymer Nanoparticles Efficiently Deliver DNA Vaccine and Induce Robust Prophylactic Immunity against Spring Viremia of Carp Virus Infection

“…PLGA has been considered as an attractive carrier and adjuvant for vaccine antigens ( 12 ). PLGA NPs could prolong the antigen circulating time, as well as increase antigen stability, leading to increased immunity ( 13 ). Chitosan is a product of natural polysaccharide chitin with some acetyl groups removed, which has various well-known properties such as biodegradability, biocompatibility, nontoxicity, bioadhesion, and immune enhancement ( 14 ).…”