Phase behavior of DSPC/PEG40St mixtures at higher emulsifier contents

Abstract

Distearoyl-sn-glycero-3-phosphocholine (DSPC) and polyoxyethylene( 40)stearate (PEG 40 St) were investigated with Langmuir monolayer isotherms and Brewster angle microscopy (BAM) imaging at DSPC/PEG 40 St 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 PEG 40 St content, indicating that the PEG 40 St squeezed out whereas more emulsifier retained in the monolayer at higher PEG 40 St 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 PEG 40 St content in the monolayer. Gray scale intensities in the Brewster angle microscopy images were determined for pure DSPC and pure PEG 40 St and a scale was established to better interpret the morphologies for the mixtures. Bud and vessels formed during the PEG 40 St squeezed out upon compression. Upon expansion, PEG 40 St and DSPC is reappeared on the monolayer. When considered BAM images together with the Langmuir isotherm, PEG 40 St molecules were found to be well distributed within the DSPC molecules at lower DSPC/PEG 40 St mole ratios and mostly phase separated at higher mole ratios. It was concluded that higher PEG 40 St content would be advantageous for the design of an efficient and cheaper ultrasound contrast agents. A lipid-to-emulsifier mole ratio of 9:1 is generally used for the microbubble composition [4,18,20,[24][25][26][27][28]. The phase formation, miscibility, and microbubble stability of this composition have still been under investigation. Emulsifier content less than 10% (9:1 mixture) is

Effect of Temperature on Stability of Lipid Microbubbles

“…It was shown that microbubble stability can be improved by controlling the conformational changes in the PEG chain of the emulsifier by cooling down the microbubbles to desired temperature upon their production. As we have shown before, the another way to control conformational changes in the PEG chain of the emulsifier is to increase the PEG40St content in the formulation (40,41). Overall, the results suggest that the effect of the conformational changes induced by temperature in the PEG chain of the emulsifier should be taken into account for the design of more stable microbubbles.…”

“…In those studies, formation of larger dark domains surrounded by emulsifier-rich continuous phase (rich-in fluorophore and therefore brighter) during slow cooling process indicates entrapment of more emulsifier molecules between condensed phase DSPC molecules (deficient in fluorophore and therefore darker) as results of PEG chains enabling to have enough time to extend into the aqueous phase and mix with condensed DSPC molecules, as discussed above. We also showed that conformational changes in the PEG chain of the emulsifier can be controlled by increasing the PEG40St content in the formulation, leading to production of more stable microbubbles (40,41). Figure 8.…”

Corrigendum for “Intravital microscopy of localized stem cell delivery using microbubbles and acoustic radiation force” (Vol. 112, Issue 1, pp. 220–227)

“…For all experiments the unit in mg/ml was utilized and the conversion mistake only came when converting to mol% to define the ratio between the coating formulation components. The correct molecular weight of PEG-40 stearate is 2046.54 g/mol (Kilic & Bolukcu, 2018;Shen et al, 2008) The authors would like to apologize for any inconvenience caused.…”

“…For all experiments the unit in mg/ml was utilized and the conversion mistake only came when converting to mol% to define the ratio between the coating formulation components. The correct molecular weight of PEG‐40 stearate is 2046.54 g/mol (Kilic & Bolukcu, 2018; Shen et al, 2008), not 328.53 g/mol. On page 221, it should read “The coating was composed of DSPC (84.8 mol%; Sigma‐Aldrich), PEG‐40 stearate (8.2 mol%; Sigma‐Aldrich), DSPE‐PEG(2000) (5.9 mol%; Avanti Polar Lipids) and DSPE‐PEG(2000)‐biotin (1.1 mol%; Avanti Polar Lipids).” This correction does not change the conclusions published in this study.…”

Corrigendum to “In Vivo Characterization of Ultrasound Contrast Agents: Microbubble Spectroscopy in a Chicken Embryo” (Ultrasound Med Biol 2012;38:1608–1617)

“…For all experiments, the unit in mg/mL was utilized, and the conversion mistake occurred only when converting to mol% to define the ratio between the coating formulation components. The correct molecular weight of PEG-40 stearate is 2046.54 g/mol (Shen et al 2008;Kilic and Bolukcu 2018), not 328.53 g/mol. On page 1610, the sentence should read "The coating was composed of DSPC (84.8 mol%; P6517, Sigma-Aldrich, Zwijndrecht, The Netherlands); PEG-40 stearate (8.2 mol%; P3440, Sigma-Aldrich); DSPE-PEG(2000) (5.9 mol%; 880125P, Avanti Polar Lipids, Alabaster, AL, USA); and DSPE-PEG(2000)-biotin (1.1 mol%; 880129C, Avanti Polar Lipids)."…”