Phase behavior of DSPC/PEG40St mixtures at higher emulsifier contents

Abstract

Phase behaviors of 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) and polyoxyethylene(40)stearate (PEG₄₀St) were investigated with Langmuir monolayer isotherms and Brewster angle microscopy (BAM) imaging at DSPC/PEG₄₀St molar ratios ranging from 9:1 to 5:5. Two plateaus were found in the Langmuir isotherms which were relatively shorter for the 9:1 mixture and extended significantly by increasing the PEG₄₀St content, indicating that the PEG₄₀St squeezed out whereas more emulsifier retained in the monolayer at higher PEG₄₀St contents. A strong hysteresis was observed when the mixed monolayers were subjected to compression-expansion cycles. The degree of hysteresis for the first cycles also increased with increasing PEG₄₀St content in the monolayer. Gray scale intensities in the Brewster angle microscopy images were determined for pure DSPC and pure PEG₄₀St and a scale was established to better interpret the morphologies for the mixtures. Bud and vessels formed during the PEG₄₀St squeezed out upon compression. Upon expansion, PEG₄₀St and DSPC is reappeared on the monolayer. When considered BAM images together with the Langmuir isotherm, PEG₄₀St molecules were found to be well distributed within the DSPC molecules at lower DSPC/PEG₄₀St mole ratios and mostly phase separated at higher mole ratios. It was concluded that higher PEG₄₀St content would be advantageous for the design of an efficient and cheaper ultrasound contrast agents.

Keywords: Conformational change; DSPC; Emulsifier; Langmuir monolayer; Microbubble; PEG(40)St; Phospholipids; Stability; Ultrasound contrast agent.