Abstract
Blending amphiphilic copolymers and lipids constitutes a novel approach to combine the advantages of polymersomes and liposomes into a new single hybrid membrane. Efforts have been made to design stimuli-responsive vesicles, in which the membrane’s dynamic is modulated by specific triggers. In this investigation, we proposed the design of pH-responsive hybrid vesicles formulated with poly(dimethylsiloxane)-block-poly(ethylene oxide) backbone (PDMS36-b-PEO23) and cationic switchable lipid (CSL). The latter undergoes a pH-triggered conformational change and induces membrane destabilization. Using confocal imaging and DLS measurements, we interrogated the structural changes in CSL-doped lipid and hybrid polymer/lipid unilamellar vesicles at the micro- and nanometric scale, respectively. Both switchable giant unilamellar lipid vesicles (GUV) and hybrid polymer/lipid unilamellar vesicles (GHUV) presented dynamic morphological changes, including protrusions and fission upon acidification. At the submicron scale, scattered intensity decreased for both switchable large unilamellar vesicles (LUV) and hybrid vesicles (LHUV) under acidic pH. Finally, monitoring the fluorescence leakage of encapsulated calcein, we attested that CSL increased the permeability of GUV and GHUV in a pH-specific fashion. Altogether, these results show that switchable lipids provide a pH-sensitive behavior to hybrid polymer/lipid vesicles that could be exploited for the triggered release of drugs, cell biomimicry studies, or as bioinspired micro/nanoreactors.
Highlights
Liposomes were initially developed as simplified cell membrane analogs and rapidly recognized as promising vesicles for a wide range of pharmaceutical applications, especially as drug delivery carriers [1]
In order to assess the incorporation of cationic switchable lipid (CSL) in lipid and hybrid polymer/lipid membranes, we prepared a series of vesicles and assessed their hydrodynamic diameter and polydispersity index (PDI) by dynamic light scattering (DLS), their surface charge by electrophoretic light scattering (ELS), and their composition by 1 H NMR
Different types of vesicles were examined (LUV and giant unilamellar lipid vesicles (GUV) composed of POPC and CSL, on the one hand, and hybrid polymer lipid, large hybrid unilamellar vesicles (LHUV) and giant hybrid unilamellar vesicles (GHUV) composed of PDMS-b-PEO diblock copolymer, POPC and CSL, on the other hand), several common features were observed and could be attributed to the presence of the switchable lipid
Summary
Liposomes were initially developed as simplified cell membrane analogs and rapidly recognized as promising vesicles for a wide range of pharmaceutical applications, especially as drug delivery carriers [1]. More than 15 liposomal-based drug formulations have reached the market [2] (e.g., AmBisome® , Doxil® /Caelyx® , and DepoCyt® ), and, recently, lipid nanoparticles enabled the delivery of the first RNAi-based drug (OnPattro® ), which was a milestone for gene therapy [3]. Polymersomes have been developed to overcome these limitations. Similar to liposomes, such vesicles result from the self-assembly of amphiphilic copolymers, exhibiting more robust properties, such as a more stable and less permeable membrane [4].
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