Role of lipid polymorphism in acoustically sensitive liposomes

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Ultrasound (US)-triggered drug release offers tunable delivery intensity and duration.
• Conventional liposomes show limited response to acoustic energy, hindering controlled release.
• Activating drug transport requires restructuring lipid membranes to facilitate drug leakage.

Purpose of the Study:

• To engineer liposomal systems for ultrasound-triggered drug release.
• To investigate strategies for lowering the energy cost of creating membrane defects.
• To explore the role of lipid molecular shape in ultrasound-induced membrane restructuring.

Main Methods:

• Formulations included stealth moieties, cholesterol, and phospholipids.
• Small-angle X-ray scattering (SAXS) analyzed lipid systems with varying phosphatidylethanolamine (PE) content.
• Fluorescence microscopy studied giant unilamellar vesicles (GUVs) with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE).

Main Results:

• Lipid membranes without PE thinned under ultrasound, reducing bending rigidity and increasing permeability.
• Lipid systems with appropriate PE content transformed from lamellar structures to reversed-type lipid tubes after ultrasound exposure.
• Ultrasound induced restructuring in DOPE-comprising GUVs, leading to a 'pearl-necklace' configuration.

Conclusions:

• Introducing lipids prone to non-lamellar structures lowers the energy barrier for ultrasound-induced membrane defects.
• PE content is critical for achieving ultrasound-triggered topological transformation of lipid membranes.
• Curvature-driven lipid sorting and membrane instabilities contribute to ultrasound-induced vesicle pearling.