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Asymmetric Lipid Bilayer01:35

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Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
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Switchable Lipids: From Conformational Switch to Macroscopic Changes in Lipid Vesicles.

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pH-switchable lipids enhance drug delivery by disrupting lipid nanoparticle assembly. Protonation upon acidification causes membrane defects, triggering cargo release without major structural changes.

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Area of Science:

  • Biochemistry
  • Materials Science
  • Nanotechnology

Background:

  • Conformationally pH-switchable lipids improve cytosolic drug delivery via lipid vesicles.
  • Understanding pH-triggered cargo release mechanisms is key for designing effective pH-switchable lipids.

Purpose of the Study:

  • To elucidate the mechanism of pH-triggered membrane destabilization and cargo release from lipid nanoparticles.
  • To investigate how pH-switchable lipids influence lipid nanoparticle assembly and membrane properties.

Main Methods:

  • Morphological analysis (FF-SEM, Cryo-TEM, AFM, confocal microscopy).
  • Physicochemical characterization (DLS, ELS).
  • Phase behavior studies (DSC, 2H NMR, Langmuir isotherm, MAS NMR).

Main Results:

  • pH-switchable lipids incorporate into lipid nanoparticles, promoting a stable liquid-ordered phase.
  • Acidification protonates switchable lipids, altering self-assembly and causing membrane fluctuations and local defects.
  • These membrane defects, not phase separation, enhance permeability and trigger cargo release.

Conclusions:

  • pH-triggered release is mediated by subtle membrane defects induced by pH-switchable lipids.
  • Rational design of pH-switchable lipids can be optimized by understanding their impact on membrane permeability.
  • This mechanism allows for cargo release without significant morphological changes in lipid vesicles.