1. Molecules. 2020 Oct 22;25(21):4882. doi: 10.3390/molecules25214882.

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.

Bayiha JC(1), Evrard B(2), Cataldo D(3), De Tullio P(4), Mingeot-Leclercq MP(1).

Author information:
(1)Cellular and Molecular Pharmacology Unit, Louvain Drug Research Institute, 
Université catholique de Louvain, Brussels 1200, Belgium, Avenue E. Mounier 73, 
B1.73.05, B-1200 Brussels, Belgium.
(2)Laboratoire de Technologie Pharmaceutique et Biopharmacie, CIRM, Université 
de Liège, 4000 Liège, Belgium.
(3)Laboratory of Tumor & Development Biology, GIGA-Cancer, Université de Liège 
and CHU, 4000 Liège, Belgium.
(4)Laboratoire de Chimie Pharmaceutique, CIRM, Université de Liège, 4000 Liège, 
Belgium.

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.

DOI: 10.3390/molecules25214882
PMCID: PMC7660049
PMID: 33105741

Conflict of interest statement: The authors declare no conflict of interest.