Memory effects of monolayers and vesicles formed by the non-ionic surfactant, 2C₁₈E₁₂

Abstract

The behaviour of monolayers and bilayers formed by the dialkyl chain non-ionic surfactant, 1,2-di-O-octadecyl-rac-glycerol-3-ω-methoxydodecaethylene glycol (2C₁₈E₁₂) in water at 297 K has been investigated. Using a surface film balance (or Langmuir trough) the compression–expansion cycle of the 2C₁₈E₁₂ monolayer was found to be reversible when compressed to surface pressures (π) less than 42 mN m⁻¹. Compression of 2C₁₈E₁₂ monolayer to π greater than 42 mN m⁻¹ above this resulted in a considerable hysteresis upon expansion with the π remaining high relative to that obtained upon compression, suggesting a time/pressure dependent re-arrangement of 2C₁₈E₁₂ molecules in the film. Morphology of the 2C₁₈E₁₂ monolayer, investigated using Brewster angle microscopy, was also found to depend upon monolayer history. Bright, randomly dispersed domains of 2C₁₈E₁₂ of approximately 5 μm in size were observed during compression of the monolayer to π less than 42 mN m⁻¹. At π of 42 mN m⁻¹ and above, the surfactant film appeared to be almost completely ‘solid-like.’ Regardless of the extent of compression of the monolayer film, expansion of the film caused formation of chains or ‘necklaces’ of individual surfactant domains, with the extent of chain formation dependent upon pressure of compression of the monolayer and the length of time held at that pressure. Irreversible effects on 2C₁₈E₁₂ vesicle size were also seen upon temperature cycling the vesicles through their liquid–crystalline phase transition temperature with vesicles shrinking in size and not returning to their original size upon standing at 298 K for periods of more than 24 h. No comparable hysteresis, time, pressure or temperature effects were observed with the monolayer or vesicles formed by the corresponding phospholipid, disteaorylphosphatidylcholine, under identical conditions. The effects observed with 2C₁₈E₁₂ are attributed to the ability of the polyoxyethylene head group to dehydrate and intrude into the hydrophobic chain region of the mono- and bilayers. These studies have important implications for the use of the vesicles formed by 2C₁₈E₁₂ as drug delivery vehicles.

Introduction

In order rationally to design new surfactants to produce vesicles with suitable properties for drug delivery it is necessary to develop an understanding of the relationship between surfactant molecular structure and aggregate architecture and behaviour. The most informative structural studies performed to date have involved the use of neutron scattering experiments and in particular neutron specular reflection and small angle neutron scattering measurements, both used in combination with isotopic substitution. By these means it has been possible to determine the detailed structure of the monolayer of the non-ionic polyoxyethylene surfactant, 2C₁₈E₁₂ at the air/water interface both in the presence and absence of cholesterol and the corresponding phospholipid, disteaorylphosphatidylcholine (DSPC) [1], [2], [3] as well as the molecular architecture of the vesicles formed from this surfactant [4], [5]. The data obtained from these studies were used to rationalise the disappointingly low encapsulation efficiency of the vesicles formed by 2C₁₈E₁₂ and guided the re-formulation of the vesicles using added cholesterol and DSPC to give considerably increased encapsulation efficiency [6]. During these studies, however, it was clear that the monolayers and bilayers (vesicles) formed by 2C₁₈E₁₂ did not behave in a reversible manner demonstrating considerable time/pressure dependent properties. In the studies reported here we use a combination of techniques to explore this behaviour with a view to understanding the potential of the vesicles formed by 2C₁₈E₁₂ as drug delivery vesicles.