Monocytic Cell-Induced Phase Transformation of Circulating Lipid-Based Liquid Crystalline Nanosystems

Abstract

Both lamellar and non-lamellar configurations are naturally present in bio-membranes, and the synthetic lipid-based liquid crystalline nano-assemblies, mimicking these unique structures, (including liposomes, cubosomes and hexosomes) are applicable in the controlled delivery of bioactives. However, it remains uncertain whether these nanosystems retain their original phase identity upon contact with blood circulating cells. This study highlights a novel biological cell flow-through approach at the synchrotron-based small angle X-ray scattering facility (bio-SAXS) to unravel their real-time phase evolution when incubated with human monocytic cells (THP-1) in suspension. Phytantriol-based cubosomes were identified to undergo monocytic cell-induced phase transformation from cubic to hexagonal phase periodicity. On the contrary, hexosomes exhibited time-dependent growth of a swollen hexagonal phase (i.e., larger lattice parameters) without displaying alternative phase characteristics. Similarly, liposomes remained undetectable for any newly evolved phase identity. Consequently, this novel in situ bio-SAXS study concept is valuable in delivering new important insights into the bio-fates of various lipid-based nanosystems under simulated human systemic conditions.

Composition-Switchable Liquid Crystalline Nanostructures as Green Formulations of Curcumin and Fish Oil

“…Due to their safety, high efficacy for drug nanoencapsulation, and low immunogenicity, lipid-based liquid crystalline carriers are gaining considerable interest in recent years. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] They are thermodynamically stable and permit development of sustained drug delivery systems in nanomedicine. 23-33 4 Lipid-based nanoparticles fabricated from biocompatible and biodegradable natural sources provide safety profiles and the possibility for engineering of green nanosystems with controlled surface area-to-volume ratios.…”

“…10,[23][24][25][26][27][28][40][41][42][43] Dispersion of nonlamellar LLC assemblies in excess water (via high-energy fragmentation involving ultrasonication, microfluidization, and homogenization methods) yields liquid crystalline nanoparticles (LCNPs). 6,[11][12][13][14][16][17][18][19][20][21][22][23][24][25][27][28][29][30][31] Lipid nanoparticles derived from bicontinuous cubic phases, called cubosomes, have much higher surface area per volume than micellar and lamellar structures. 6,14,16,23 This feature is advantageous for improving the bioavailability of encapsulated hydrophobic, hydrophilic or amphiphilic compounds.…”

“…19 Cubosomes are being intensively studied for development of drug delivery carriers with anti-inflammatory, antimicrobial, antiviral, anticancer, neuroprotective and anti-dementia activities through different kinds of administration routes (oral, intranasal, transdermal, ophthalmic, or mucosal) as well as for protection of food ingredients. 13,[18][19][20][21][22][23][24][25][26][27][28][29] The monoglyceride lipid monoolein (MO or glycerol monooleate) (Fig. 1A) is one of the key lyotropic lipids suitable for the sustainable development of liquid crystalline delivery systems.…”

“…As a matter of fact, increased bioavailability of active ingredients will essentially diminish the need for drug elimination and thus will prevent the risk for the environment. Due to their safety, high efficacy for drug nanoencapsulation, and low immunogenicity, lipid-based liquid crystalline carriers are gaining considerable interest in recent years. − They are thermodynamically stable and permit the development of sustained drug delivery systems in nanomedicine. − …”

“…Dispersion of nonlamellar LLC assemblies in excess water (via high-energy fragmentation involving ultrasonication, microfluidization, and homogenization methods) yields liquid crystalline nanoparticles (LCNPs). ,− ,− ,− Lipid nanoparticles derived from bicontinuous cubic phases, called cubosomes, have a much higher surface area per volume than micellar and lamellar structures. ,,, This feature is advantageous for improving the bioavailability of encapsulated hydrophobic, hydrophilic, or amphiphilic compounds . Cubosomes are being intensively studied for the development of drug delivery carriers with anti-inflammatory, antimicrobial, antiviral, anticancer, neuroprotective, and antidementia activities through different kinds of administration routes (oral, intranasal, transdermal, ophthalmic, or mucosal) as well as for protection of food ingredients. ,− The monoglyceride lipid monoolein (MO or glycerol monooleate) (Figure A) is one of the key lyotropic lipids suitable for the sustainable development of liquid crystalline delivery systems. ,− , It is a nonlamellar lipid, which is a nontoxic, biodegradable, and biocompatible material, classified as GRAS (generally recognized as safe). , …”