Nanostructured aqueous dispersions of citrem interacting with lipids and PEGylated lipids

Abstract

We report on the formation of nanostructured aqueous dispersions based on the negatively charged food-grade emulsifier citrem (citric acid esters of mono- and diglycerides). To our knowledge, this is the first report in the literature on the spontaneous formation of aqueous PEGylated and non-PEGylated dispersions of citrem. Citrem can be easily dispersed in water in the absence of other surfactant-like lipids without applying high-energy input. However, to investigate the stability and to characterize the internal structure of dispersions with a narrow size distribution, ultrasonication was applied for the emulsification of citrem or its binary mixture with PEGylated lipids of poly (ethylene glycol) monooleate with M_n ∼ 460 (MO-PEG₄₆₀) or M_n ∼ 860 (MO-PEG₈₆₀) and non-PEGylated lipids (monoolein (MO) or phytantriol (PHYT)). We obtained stable dispersions (>4 months) consisting of particles with highly negative zeta potentials (in the range of −41–−31 mV) and a mean particle size range of 139–172 nm. A decrease in the particle mean size by 13–19% was observed when dispersing citrem in the presence of a PEGylated monoolein (either MO-PEG₈₆₀ or MO-PEG₄₆₀). The structural characterization was studied by synchrotron small angle X-ray scattering (SAXS), where the effect of partial replacement of citrem by two PEGylated lipids or other well-known lipids (MO and PHYT) was investigated. In addition, cryogenic transmission electron microscopy (cryo-TEM) was applied to characterize the morphology and the internal structure of different PEGylated dispersions of citrem. The cryo-TEM revealed particles enveloping internal structures in co-existence with vesicles. No long-range order was observed, in correlation with the results obtained by SAXS, suggesting that the particles were comprised of the internal reverse micellar (L₂) phase. Based on the SAXS results, the partial replacement of citrem by high amount of MO or PHYT induced the formation of hexosomes. The investigated dispersions of citrem could be attractive as nanocarriers of poorly water-soluble drugs and functional foods.