학술논문
Switchable Lipids: From Conformational Switch to Macroscopic Changes in Lipid Vesicles.
Document Type
Academic Journal
Author
Phan HT; Faculty of Pharmacy, University of Montreal, Montréal H3C 3J7, Canada.; Passos Gibson V; Faculty of Pharmacy, University of Montreal, Montréal H3C 3J7, Canada.; Guédin A; University of Bordeaux, CNRS, INSERM, ARNA, UMR 5320, U1212, Bordeaux F-33000 France.; Ibarboure E; Laboratoire de Chimie des Polymères Organiques LCPO Université de Bordeaux CNRS Bordeaux INP UMR 5629, Pessac F-33600, France.; El Mammeri N; Institut de Chimie et de Biologie des Membranes et des Nano-objets, Institut Européen de Chimie et Biologie, CNRS, UMR 5248, Université de Bordeaux, Pessac F-33600, France.; Grélard A; Institut de Chimie et de Biologie des Membranes et des Nano-objets, Institut Européen de Chimie et Biologie, CNRS, UMR 5248, Université de Bordeaux, Pessac F-33600, France.; Le Meins JF; Laboratoire de Chimie des Polymères Organiques LCPO Université de Bordeaux CNRS Bordeaux INP UMR 5629, Pessac F-33600, France.; Dufourc EJ; Institut de Chimie et de Biologie des Membranes et des Nano-objets, Institut Européen de Chimie et Biologie, CNRS, UMR 5248, Université de Bordeaux, Pessac F-33600, France.; Loquet A; Institut de Chimie et de Biologie des Membranes et des Nano-objets, Institut Européen de Chimie et Biologie, CNRS, UMR 5248, Université de Bordeaux, Pessac F-33600, France.; Giasson S; Faculty of Pharmacy, University of Montreal, Montréal H3C 3J7, Canada.; Department of Chemistry, University of Montreal, Montréal H3C 3J7, Canada.; Leblond Chain J; University of Bordeaux, CNRS, INSERM, ARNA, UMR 5320, U1212, Bordeaux F-33000 France.
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
Subject
Language
English
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.