Abstract
Lamellar and non-lamellar liquid crystalline nanodispersions, including liposomes, cubosomes, and hexosomes are attractive platforms for drug delivery, bio-imaging, and related pharmaceutical applications. As compared to liposomes, there is a modest number of reports on the continuous production of cubosomes and hexosomes. Using a binary lipid mixture of citrem and soy phosphatidylcholine (SPC), we describe the continuous production of nanocarriers for delivering thymoquinone (TQ, a substance with various therapeutic potentials) by employing a commercial microfluidic hydrodynamic flow-focusing chip. In this study, nanoparticle tracking analysis (NTA) and synchrotron small-angle X-ray scattering (SAXS) were employed to characterize TQ-free and TQ-loaded citrem/SPC nanodispersions. Microfluidic synthesis led to formation of TQ-free and TQ-loaded nanoparticles with mean sizes around 115 and 124 nm, and NTA findings indicated comparable nanoparticle size distributions in these nanodispersions. Despite the attractiveness of the microfluidic chip for continuous production of citrem/SPC nano-self-assemblies, it was not efficient as comparable mean nanoparticle sizes were obtained on employing a batch (discontinuous) method based on low-energy emulsification method. SAXS results indicated the formation of a biphasic feature of swollen lamellar (Lα) phase in coexistence with an inverse bicontinuous cubic Pn3m phase in all continuously produced TQ-free and TQ-loaded nanodispersions. Further, a set of SAXS experiments were conducted on samples prepared using the batch method for gaining further insight into the effects of ethanol and TQ concentration on the structural features of citrem/SPC nano-self-assemblies. We discuss these effects and comment on the need to introduce efficient microfluidic platforms for producing nanocarriers for delivering TQ and other therapeutic agents.
Highlights
Cubosomes and hexosomes are analogous to liposomes, which are widely used as drug nanocarriers since their discovery a half-century ago [1], but have different structural properties as they envelope three- (3D) and two-dimensional (2D) self-assembled interiors, respectively [2,3,4,5,6,7,8,9,10,11,12]
We report on continuous production of citrem/soy phosphatidylcholine (SPC) nano-selfassemblies by using a commercial hydrodynamic flow focusing (HFF) microfluidic chip, and explore the possible use of these nano-self-assemblies as nanocarriers for delivering thymoquinone (TQ), which is the main therapeutic compound (30–48%) of the essential volatile oil of Nigella sativa and has wide therapeutic potentials [16,50,51]
These mean sizes and modes were comparable with those previously reported for ethanol-free citrem/SPC nanodispersions prepared at same citrem/SPC lipid composition by using two different batch methods: a low-energy emulsification method and a high-energy emulsification method based on ultrasonication [30,33]
Summary
Cubosomes and hexosomes are analogous to liposomes, which are widely used as drug nanocarriers since their discovery a half-century ago [1], but have different structural properties as they envelope three- (3D) and two-dimensional (2D) self-assembled interiors, respectively [2,3,4,5,6,7,8,9,10,11,12]. Nanomaterials 2021, 11, 1510 of these lipid nanoparticles and related nano-self-assemblies including micellar cubosomes and emulsified microemulsions (EMEs) is linked to their capability of loading drugs and imaging agents with different physiochemical properties [3,5,13,14,15,16,17,18,19,20,21]. For evaluating the efficiency of the microfluidic platform at same ethanol concentrations and lipid compositions, the mean nanoparticle sizes and size distributions of two selected continuously produced citrem/SPC nanoparticles were compared with those generated by using a batch emulsification method The latter method is based on vortexing the binary citrem/SPC mixtures in excess water for 5 min (samples A9 and A10, Table 1). 1.9 wt%, respectively. b Samples A9 and A10 were not investigated (N.I.). c Mean and mode nanoparticle sizes are presented with standard deviations and standard errors, respectively
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