Non-Lamellar Liquid Crystalline Nanocarriers for Thymoquinone Encapsulation

Abstract

Owing to their unique structural features, non-lamellar liquid crystalline nanoparticles comprising cubosomes and hexosomes are attracting increasing attention as versatile investigative drug carriers. Background: Depending on their physiochemical characteristics, drug molecules on entrapment can modulate and reorganize structural features of cubosomes and hexosomes. Therefore, it is important to assess the effect of guest molecules on broader biophysical characteristics of non-lamellar liquid crystalline nanoparticles, since drug-induced architectural, morphological, and size modifications can affect the biological performance of cubosomes and hexosomes. Methods: We report on alterations in morphological, structural, and size characteristics of nanodispersions composed from binary mixtures of glycerol monooleate and vitamin E on thymoquinone (a molecule with wide therapeutic potentials) loading. Results: Thymoquinone loading was associated with a slight increase in the mean hydrodynamic nanoparticle size and led to structural transitions from an internal biphasic feature of coexisting inverse cubic Fd3m and hexagonal (H2) phases to an internal inverse cubic Fd3m phase (micellar cubosomes) or an internal inverse micellar (L2) phase (emulsified microemulsions, EMEs). We further report on the presence of “flower-like” vesicular populations in both native and drug-loaded nanodispersions. Conclusions: These nanodispersions have the potential to accommodate thymoquinone and may be considered as promising platforms for the development of thymoquinone nanomedicines.

Nanoliposomes and Tocosomes as Multifunctional Nanocarriers for the Encapsulation of Nutraceutical and Dietary Molecules

“…Successful nanoliposomal formulations of TQ have been reported exhibiting ideal particle characterization (with respect of size and zeta potential) as well as high loading capacity (i.e., around 75%) [31]. More recently, Yaghmur and co-workers formulated nanodispersions composed from binary mixtures of glycerol monooleate and vitamin E stabilized with d-α-tocopheryl poly (ethylene glycol) succinate (TPGS-PEG 2000 ) for the encapsulation of thymoquinone [134,135]. The produced nanoparticles were in the form of micellar cubosomes with an internal inverse cubic Fd3m phase and emulsified microemulsions (EMEs) with an internal inverse microemulsion.…”

“…Authors reported the presence of "flower-like" vesicular populations in both native and drug-loaded nanodispersions. They concluded that the nanodispersions have the potential to accommodate thymoquinone and can be considered as promising formulations for the development of thymoquinone nanomedicines [134,135].…”

Advances in the Design of pH-Sensitive Cubosome Liquid Crystalline Nanocarriers for Drug Delivery Applications

“…Lipid nanoparticle-mediated drug delivery experiences rapid developments in the field of liquid crystalline colloidal carriers, e.g., cubosomes, spongosomes, hexosomes and vesicles [1][2][3][4][5][6][7]. In addition to the expansion of liposomes as advanced drug delivery systems [8][9][10], a plethora of research has been dedicated to diverse mesoporous liquid crystalline materials and nanostructures intended as drug delivery devices [11][12][13][14][15][16].…”

Continuous Microfluidic Production of Citrem-Phosphatidylcholine Nano-Self-Assemblies for Thymoquinone Delivery

“…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]. In the development of nanocarriers for drug delivery, the attractiveness Nanomaterials 2021, 11, 1510 2 of 16 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]. The localization of these agents in the nanoparticles' interiors is governed by a set of complex interactions of the loaded guest molecules with the main lipid constituents and water [3,6,13,15,[22][23][24][25][26].…”

“…In the following, we report on continuous production of citrem/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]. In literature, various nanoparticles including liposomes [52], micellar cubosomes [16], niosomes [53], and albumin [54] nanoparticles were suggested for delivering TQ and overcoming different reported limitations (including poor bioavailability and membrane penetration ability) [16,54]. In the present study, we report also on the effects of ethanol concentration and lipid composition on the structural features and size characteristics of the continuously produced citrem/SPC nanoparticles (samples A1-A8, Table 1) by using synchrotron small-angle X-ray scattering (SAXS) and nanoparticle tracking analysis (NTA), respectively.…”