Changes in membrane biophysical properties induced by the Budesonide/Hydroxypropyl-β-cyclodextrin complex.

Area of Science:

• Biophysics
• Pharmacology
• Cell Biology

Background:

• Budesonide (BUD) is a poorly soluble anti-inflammatory drug for asthma and COPD.
• Hydroxypropyl-β-cyclodextrin (HPβCD) is a drug-solubilizing agent that interacts with cholesterol.
• BUD complexed with HPβCD (BUD:HPβCD) shows enhanced anti-inflammatory effects in COPD models.

Purpose of the Study:

• To investigate the effect of BUD:HPβCD on the biophysical properties of membrane lipids.
• To explore the role of cholesterol-enriched lipid domains in the therapeutic action of BUD:HPβCD.

Main Methods:

• Cellular models (A549 lung epithelial cells) were used to assess cholesterol extraction.
• Large unilamellar vesicles (LUVs) with fluorescent probes (DPH, calcein) measured membrane fluidity and permeability.
• Giant unilamellar vesicles (GUVs) and lipid monolayers analyzed the disruption of cholesterol-enriched domains and lipid packing.

Main Results:

• BUD:HPβCD and HPβCD extracted cholesterol from A549 cells.
• BUD:HPβCD increased membrane fluidity and permeability in cholesterol-containing LUVs.
• BUD:HPβCD disrupted cholesterol-enriched raft-like domains in GUVs and altered lipid packing/desorption in monolayers, with enhanced effects compared to HPβCD alone.

Conclusions:

• BUD:HPβCD alters the biophysical properties of cholesterol-enriched membrane domains.
• These alterations include increased membrane fluidity and permeability, and disruption of lipid raft domains.
• The enhanced therapeutic effects of BUD:HPβCD may be partly mediated by modulating these cholesterol-dependent membrane domains.