The Budesonide-Hydroxypropyl-β-Cyclodextrin Complex Attenuates ROS Generation, IL-8 Release and Cell Death Induced by Oxidant and Inflammatory Stress. Study on A549 and A-THP-1 Cells

Abstract

Synthetic glucocorticoids such as budesonide (BUD) are potent anti-inflammatory drugs commonly used to treat patients suffering from chronic inflammatory diseases. A previous animal study reported a higher anti-inflammatory activity with a 2-hydroxypropyl-β-cyclodextrin (HPβCD)-based formulation of BUD (BUD:HPβCD). This study investigated, on cellular models (A549 and A-THP-1), the effect of BUD:HPβD in comparison with BUD and HPβCD on the effects induced by oxidative and inflammatory stress as well as the role of cholesterol. We demonstrated the protective effect afforded by BUD:HPβCD against cytotoxicity and ROS generation induced by oxidative and inflammatory stress. The effect observed for BUD:HPβCD was comparable to that observed with HPβCD with no major effect of cholesterol content. We also demonstrated (i) the involvement of the canonical molecular pathway including ROS generation, a decrease in PI3K/Akt activation, and decrease in phosphorylated/unphosphorylated HDAC2 in the effect induced by BUD:HPβCD, (ii) the maintenance of IL-8 decrease with BUD:HPβCD, and (iii) the absence of improvement in glucocorticoid insensitivity with BUD:HPβCD in comparison with BUD, in conditions where HDAC2 was inhibited. Resulting from HPβCD antioxidant and anticytotoxic potential and protective capacity against ROS-induced PI3K/Akt signaling and HDAC2 inhibition, BUD:HPβCD might be more beneficial than BUD alone in a context of concomitant oxidative and inflammatory stress.

Rescuing a Troubled Tolcapone with PEGylated PLGA Nanoparticles: Design, Characterization, and Hepatotoxicity Evaluation

“…As suggested by other authors, HPβCD can reduce ROS production via cholesterol depletion in oxidative stress-induced cells. 39,40 As tolcapone showed to induce lipid accumulation in hepatic cells by promoting hepatocellular triglyceride accumulation in another study, we hypothesize that HPβCD might have a role in lipid metabolism, protecting the cells from impairments caused by drugs. 13 For the moment, and to the best of our knowledge, the exact mechanisms of how HPβCD, and cyclodextrin, in general, protects cells remain elusive.…”

“…Indeed other works have pointed out that HPβCD can reduce ROS production via cholesterol depletion in oxidative stress-induced cells, thus exhibiting antioxidant and anticytotoxic properties. 39,40 The PLGA-GAL@Tolc formulation was unable to reduce ROS production in both media, except for the formulation tested at 50 μM in glucose medium (Figure 7a), where ROS production was increased. These results suggest that HPβCD might have a dual function in the formulation: cryoprotection of NPs and an anticytotoxic effect, protecting cells from tolcapone ROSinduced aggression.…”

Isolated Compounds from Buddleja Coriacea with Antibacterial and Anti-Inflammatory Activities in the Urinary Tract

“…Finally, regarding the anti-inflammatory activity of the isolated compounds, compound 1 is a glucocorticoid with powerful antiinflammatory effects [38] that is used to treat chronic inflammatory diseases [39]. However, although compound 1 was isolated as a mixture of diastereoisomers, they do not show significant structural differences, so the activity of both structures can be assumed to be similar.…”

Bilosomes and Biloparticles for the Delivery of Lipophilic Drugs: A Preliminary Study

“…For instance, NLRP3, one of the most well-known inflammasomes, has been shown to mediate the inflammatory response in intestinal disorders via an oxidative stress mechanism [63][64][65]. Thus, to understand whether the NLRP3 inflammasome could be activated in human intestinal cells in response to an oxidative stimulus, and to evaluate whether formulations containing budesonide could prevent an oxidative stress-related inflammatory response, as already evidenced [66], we triggered CaCo2 cells with the oxidoreductase enzyme glucose oxidase (GO), able to induce the production of hydrogen peroxide (H 2 O 2 ) via glucose oxidation as previously described [67].…”