Microfluidic technologies for the synthesis and manipulation of biomimetic membranous nano-assemblies

Pilkington, Colin P; Seddon, John M.; Elani, Yuval

doi:10.1039/d0cp06226j

Cited by 24 publications

(32 citation statements)

References 134 publications

(210 reference statements)

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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. 5,[10][11][12][13][14][15][16][17]23 Such particles can be formed by dispersion of lipid-based lyotropic liquid crystalline (LLC) phases, which spontaneously self-assemble upon exposure of lyotropic lipids to water. 11,17 The formation of lamellar (L α /L c ), bicontinuous cubic (V 2 ), inverted hexagonal (H II ), sponge (L 3 ), fluid isotropic (L 2 ) or micellar cubic (I2) mesophases 6,10,[14][15][16][17][25][26][27][28][29][30] has been rationalized through the critical packing parameter (CPP).…”

Section: Introductionmentioning

confidence: 99%

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

Rakotoarisoa

Angelov

Espinoza

et al. 2021

ACS Sustainable Chem. Eng.

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Green compositions and processes for fabrication of dual-and multi-loaded nanocarriers with antioxidant functionality and neuroprotective, cardioprotective, antiviral, and antiproliferative activities are of broad interest for innovations in pharmaceutics and nutraceutics. Co-encapsulation of curcumin (studied as a key multipurpose phytochemical antioxidant) with ω-3 polyunsaturated fatty acids (PUFAs) (studied as active ingredients of natural fish oil) may increase the oxidative stability of selfassembled formulations aiming at development of "food drugs" and prevention of disease progression in various pathological states. The objective of this work is to prepare selfassembled lyotropic liquid crystalline nanostructures as dual-loaded biodegradable carriers of ω-3 PUFA-fish oil and curcumin. A detailed structural phase diagram of ternary [monoolein (MO) -PEGylated lipid mixture] / [fish oil -curcumin] / water system is created. A composition-mediated switch between nanostructures of different topologies and polymorphic states is achieved through varying the ratios between the amphiphilic monoglyceride ingredient, fish oil and water, which yielded cubic, sponge, and lamellar mesophases of tunable nanoscale repeat spacings. Synchrotron small-angle X-ray scattering (SAXS) studies are performed with the lyotropic liquid crystalline nanostructures along compositional dilution lines. The temperature effect is examined at 22 °C and 5 °C with regard to preparation conditions and mesophase stability on storage.Bulk mesophases are dispersed into lipid nanoparticles at 22 °C, the structures and topologies of which are revealed by SAXS and cryo-transmission electron microscopy (cryo-TEM) imaging. The new knowledge about the controlled multicomponent 3 supramolecular assembly and the achieved stabilization of low-temperature cubic phases (hydrated in 5 wt% D-(+)-glucose) should facilitate the development of cost-effective stable and safe delivery systems of weakly soluble natural antioxidant compounds coencapsulated with ω-3 PUFA oils.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Rakotoarisoa

Angelov

Espinoza

et al. 2021

ACS Sustainable Chem. Eng.

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“…[ 184 ] The process by which the liposomes self‐assemble in this MHF device is based on the reciprocal diffusion of alcohol/lipid and water at the downstream interface formed within the central channel of the chip, as shown in ( Figure 5 a ). [ 185 ] Following studies determined the parameters of MHF devices that influence the diameter, dispersity and production rate of liposomes. Such parameters include the width of the alcohol stream, [ 186 ] downstream turbulence, [ 187 ] flow rate ratio, [ 188 ] and width to height ratio of the microfluidic channels.…”

Section: Drug Delivery Systems and Droplet‐based Technologymentioning

confidence: 99%

Section: Drug Delivery Systems and Droplet‐based Technologymentioning

confidence: 99%

Droplet Microfluidics for Tumor Drug‐Related Studies and Programmable Artificial Cells

Dimitriou

Tornillo

et al. 2021

Global Challenges

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(1 of 17)www.global-challenges.com robotics, have promoted the use of in vitro tumor models in high-throughput drug screenings. [2,3] High-throughput screens for anticancer drugs have been, for a long time, limited to 2D culture of tumor cells, grown as a monolayer on the bottom of a well of a microtiter plate. Compared to 2D cell cultures, 3D culture systems can more faithfully model cell-cell interactions, matrix deposition and tumor microenvironments, including more physiological flow conditions, oxygen and nutrient gradients. [4] Therefore, 3D cultures have recently begun to be incorporated into high-throughput drug screenings, with the aim of better predicting drug efficacy and improving the prioritization of candidate drugs for further in vivo testing in animals.Because of the relatively simple, reproducible, amenable to automation and scalable culture methods, single-cell type and mixed-cell tumor spheroids, known as multicellular tumor spheroids (MCTSs), are used as 3D models. [5] There exists a broad range of natural hydrogels that are compatible with microfluidics, and which provide cancer cells with mechanical cues and adhesion sites to proliferate and grow into MCTSs. [6] With the aid of microfluidics and development of more complex 3D tumor models, [7,8] and the large-scale production of tumor spheroids in hydrogels, the number of compounds that could progress to in vivo testing could be restricted, thus reducing the number of animals needed for preclinical studies.Tumor-targeted drug delivery using microparticles and liposomes is beneficial compared to conventional drug administration. This is because encapsulated drug dosages can be controlled, healthy tissues can remain unharmed during treatment and drug resistance of cancer cells may be reduced/ prevented. [9,10] Microparticles and liposomes can be tailored to specifically target tumor sites using molecular conjugates, while avoiding toxic effects. [9] This review discusses the application of droplet-based microfluidic technologies for the development of accurate in vitro tumor models and improved cancer treatment strategies. The first part of the review centers around the generation of MCTSs in natural hydrogels for a better recapitulation of the in vivo tumor microenvironment. The second section is focused on microparticle and liposomal production for tumor-targeted drug delivery. Emphases is given to microfluidic methodologies for the production of these systems, and the potential of compartmentalized artificial cells as anticancer drug screening platforms.

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“…Unlike liposomes [35][36][37][38][39][40] and other lipid nanoparticles [41][42][43], the continuous microfluidic synthesis of cubosomes, hexosomes, and other related nano-self-assemblies is rarely investigated [44,45]. Among different microfluidic mixers, hydrodynamic flow focusing (HFF) microfluidic platforms are the most employed for the continuous production of these nanoparticles [35,39,[46][47][48][49]. They are attractive for use owing to their capability of controlling the mean nanoparticle size and size distribution by creating a well-defined and predictable interfacial region between the injected fluids, and hydrodynamically focusing of the centre and side streams to submicrometer-sized dimensional scales for rapid mixing and patterning [35,[38][39][40]45].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Microfluidic technologies for the synthesis and manipulation of biomimetic membranous nano-assemblies

Abstract: A mini-review of microfluidic technologies for the generation and manipulation of biomimetic nano-assemblies, including perspectives for future research directions.

Cited by 24 publications

References 134 publications

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

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

Droplet Microfluidics for Tumor Drug‐Related Studies and Programmable Artificial Cells

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

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