Switchable Lipids: From Conformational Switch to Macroscopic Changes in Lipid Vesicles.

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  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 9882736 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5827 (Electronic) Linking ISSN: 07437463 NLM ISO Abbreviation: Langmuir Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Chemical Society, c1985-
    • Subject Terms:
      Lipids*/chemistry ; Drug Delivery Systems*; Chemical Phenomena ; Molecular Conformation ; Permeability
    • Abstract:
      It has been shown that the use of conformationally pH-switchable lipids can drastically enhance the cytosolic drug delivery of lipid vesicles. Understanding the process by which the pH-switchable lipids disturb the lipid assembly of nanoparticles and trigger the cargo release is crucial to optimize the rational design of pH-switchable lipids. Here, we gather morphological observations (FF-SEM, Cryo-TEM, AFM, confocal microscopy), physicochemical characterization (DLS, ELS), as well as phase behavior studies (DSC, 2 H NMR, Langmuir isotherm, and MAS NMR) to propose a mechanism of pH-triggered membrane destabilization. We demonstrate that the switchable lipids are homogeneously incorporated with other co-lipids (DSPC, cholesterol, and DSPE-PEG 2000 ) and promote a liquid-ordered phase insensitive to temperature variation. Upon acidification, the protonation of the switchable lipids triggers a conformational switch altering the self-assembly properties of lipid nanoparticles. These modifications do not lead to a phase separation of the lipid membrane; however, they cause fluctuations and local defects, which result in morphological changes of the lipid vesicles. These changes are proposed to affect the permeability of vesicle membrane, triggering the release of the cargo encapsulated in the lipid vesicles (LVs). Our results confirm that pH-triggered release does not require major morphological changes, but can result from small defects affecting the lipid membrane permeability.
    • Accession Number:
      0 (Lipids)
    • Publication Date:
      Date Created: 20230216 Date Completed: 20230301 Latest Revision: 20230412
    • Publication Date:
      20231215
    • Accession Number:
      10.1021/acs.langmuir.2c03149
    • Accession Number:
      36793207