Abstract

Lipid vesicles are an important class of biomaterials that have a wide range of applications, including drug delivery, cosmetic formulations and model membrane platforms on solid supports. Depending on the application, properties of a vesicle population such as size distribution, charge and permeability need to be optimized. Preparation methods such as mechanical extrusion and sonication play a key role in controlling these properties, and yet the effects of vesicle preparation method on vesicular properties and integrity (e.g., shape, size, distribution and tension) remain incompletely understood. In this study, we prepared vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid by either extrusion or sonication, and investigated the effects on vesicle size distribution over time as well as the concomitant effects on the self-assembly of solid-supported planar lipid bilayers. Dynamic light scattering (DLS), quartz crystal microbalance with dissipation (QCM-D) monitoring, fluorescence recovery after photobleaching (FRAP) and atomic force microscopy (AFM) experiments were performed to characterize vesicles in solution as well as their interactions with silicon oxide substrates. Collectively, the data support that sonicated vesicles offer more robust control over the self-assembly of homogenous planar lipid bilayers, whereas extruded vesicles are vulnerable to aging and must be used soon after preparation.

Highlights

  • Synthetic lipid vesicles are topologically closed assemblies of single or multiple lipid bilayers that are increasingly important biomaterials for a wide range of delivery and formulation applications in the pharmaceutical and cosmetic industries, among other fields [1,2,3]

  • We found that while vesicles prepared by sonication formed homogenous planar bilayers through an identical self-assembly pathway regardless of aging conditions, vesicles prepared by mechanical extrusion exhibited age-dependent self-assembly interaction kinetics, but the quality of the planar bilayer formed deteriorated as a function of the age of the precursor vesicles

  • The combination of biophysical and surface-sensitive analytical techniques employed in this study provides evidence that the process of vesicle aging can affect the quality and functional properties of solid-supported planar lipid bilayers

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Summary

Introduction

Synthetic lipid vesicles ( referred to as liposomes) are topologically closed assemblies of single or multiple lipid bilayers that are increasingly important biomaterials for a wide range of delivery and formulation applications in the pharmaceutical and cosmetic industries, among other fields [1,2,3]. Homogenous samples and stringent quality control are key target goals of any manufacturing protocol, and a handful of preparation techniques, including sonication and mechanical extrusion, meet these criteria and are widely used in academia and industry [4,5,6]. Extrusion can produce monodisperse unilamellar vesicle suspensions as a result of energy-dissipating shearing forces that are generated when lipid suspensions are repeatedly passed through polymer membranes containing well-defined, nanoscale pores under high-pressure conditions [8,9]. The administration time and the intensity of the pressure waves largely determine the size of the processed vesicles, and in general sonication is quicker and less-intensive than extrusion [10,11]

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