Lipid Vesicle Preparation Using W/O/W Multiple Emulsions Via Solvent Evaporation: The Effect of Emulsifiers on the Entrapment Yield of Hydrophilic Materials

Abstract

We studied the effects of emulsifiers on the entrapment yields of a hydrophilic material, calcein, in lipid vesicles formed using the multiple emulsion method. The primary emulsion (W 1 /O) was prepared via sonication while the secondary emulsification that produced the W 1 /O/W 2 multiple emulsions was achieved using the microchannel (MC) emulsification technique. The emulsifiers used in the continuous (W 2 ) phase were Tween ® 80, Pluronic ® F68, and bovine serum albumin (BSA). Lipid vesicles formed via solvent evaporation of the multiple emulsion droplets had an average diameter of about 180 nm, similar to the size of the water droplets in the primary W 1 /O emulsions. The entrapment yields of calcein increased with decreasing concentrations of Tween ® 80 but decreased with decreasing concentrations of Pluronic ® F68 and BSA. The effects of type and concentration of emulsifier were considered in relation to three possible mechanisms: (i) destabilization/solubilization of lipid bilayers by emulsifiers, (ii) reversed-micellar transport of W 1 contents from internal to external water phases through the O phase, and (iii) release of inner water (W 1 ) contents into the continuous (W 2 ) phase via the instability of W 1 /O/W 2 and leakage of W 1 contents. Using the food grade emulsifier Tween ® 80 at a low concentration of about 0.1 or 0.05 wt%, calcein as a model hydrophilic material could be efficiently entrapped (ca. 80%) in homogenously dispersed lipid vesicles.

Potential Enhancement of Metformin Hydrochloride in Lipid Vesicles Targeting Therapeutic Efficacy in Diabetic Treatment

“…According to Kuroiwa et al [22], the use of 3.0 wt % (w/v) Tween ® 80 with a relative molecular weight of 1310 as an emulsifier in the external water phase resulted in an entrapment yield of as low as 20% for calcein. Previously, Ossai et al [23] suggested that the entrapment yield of calcein increased with a decrease in Tween 80 concentration, which conforms with our present study in which an appreciable entrapment of 40.12% for MH was obtained at low concentration (0.1 wt %) of Tween ® 80 as the external water phase emulsifier. The lower entrapment yields of the current work's formulation compared with that previously established by Ossai et al [23], specific to the entrapment of calcein, could be due to either efflux or leakage of the entrapped material from the internal aqueous phase to the continuous aqueous phase, which might have partially taken place as the solvent evaporation proceeded.…”

“…Previously, Ossai et al [23] suggested that the entrapment yield of calcein increased with a decrease in Tween 80 concentration, which conforms with our present study in which an appreciable entrapment of 40.12% for MH was obtained at low concentration (0.1 wt %) of Tween ® 80 as the external water phase emulsifier. The lower entrapment yields of the current work's formulation compared with that previously established by Ossai et al [23], specific to the entrapment of calcein, could be due to either efflux or leakage of the entrapped material from the internal aqueous phase to the continuous aqueous phase, which might have partially taken place as the solvent evaporation proceeded. Specifically, the lower relative molecular weight of MH (165.6 g/mol) might be an explanation for this occurrence (of efflux or leakage of the entrapped material), compared with that of calcein (622.6 g/mol), of the current work.…”

“…In the current work, the size distribution of the W 1 /O/W 2 multiple emulsion droplets (refer to Figure 1 ) ranged from 35 to 72 mm with an average size of 52 mm. This was comparable to multiple emulsion droplet sizes in our previous report [ 23 ], specifically for the entrapment of calcein in lipid vesicles. The size of the lipid vesicles is of great importance in terms of their application as carrier vehicles for drug delivery [ 24 ].…”

Preparation and characterization of W1/O/W2 emulsions stabilized by glycated and heat‐modified egg white proteins

“…Different kinds of emulsification devices can be used to form W 1 /O/W 2 emulsions, including high‐pressure valve homogenization (HPVH), microfluidization, sonication, high‐speed shearing and membrane homogenization 8‐10 . Often, a relatively high‐intensity method (such as HPVH, microfluidization and sonication) is used to form W 1 /O emulsions containing small water droplets dispersed in oil, then a relatively low‐intensity method (such as high‐speed shearing or membrane homogenization) is used to form the W 1 /O/W 2 emulsions.…”

“…Different kinds of emulsification devices can be used to form W 1 /O/W 2 emulsions, including high-pressure valve homogenization (HPVH), microfluidization, sonication, high-speed shearing and membrane homogenization. [8][9][10] Often, a relatively highintensity method (such as HPVH, microfluidization and sonication) is used to form W 1 /O emulsions containing small water droplets dispersed in oil, then a relatively low-intensity method (such as high-speed shearing or membrane homogenization) is used to form the W 1 /O/W 2 emulsions. However, in some cases it is also possible to use the same homogenizer but operated at different intensities, such as creating the W 1 /O emulsions using a high operating pressure, then creating the W 1 /O/W 2 emulsions using a lower operating pressure with the same HPVH.…”