Comparison of bulk and microfluidic methods to monitor the phase behaviour of nanoparticles during digestion of lipid-based drug formulations using <i>in situ</i> X-ray scattering

Hong, Linda; Şeşen, Muhsincan; Hawley, Adrian; Neild, Adrian; Spicer, Patrick T.; Boyd, Ben J.

doi:10.1039/c9sm01440c

Cited by 13 publications

(7 citation statements)

References 37 publications

(52 reference statements)

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“…In a recent study, Boyd and co-workers [ 52 ] reported on online characterization of lipid formulations during their digestion through coupling a simple T-junction microcapillary system, HFF microfluidic chip ( Figure 2 F), or pH-stat apparatus to synchrotron SAXS. They reported on the suitability of both microfluidic devices for the in situ SAXS characterization investigations of lipid nanoparticulate formulations.…”

Section: Continuous Production and In Situ Characterization Of Nano-s...mentioning

confidence: 99%

“…They reported on the suitability of both microfluidic devices for the in situ SAXS characterization investigations of lipid nanoparticulate formulations. Figure 2 G shows the SAXS patterns at different reaction times, indicating the generation of an inverse cubic Pn3m phase on digesting a lipid formulation containing phytantriol [ 52 ].…”

Section: Continuous Production and In Situ Characterization Of Nano-s...mentioning

confidence: 99%

“…Here, 2D and 3D microfluidic platforms are attractive for real-time tracking analysis of nucleation and monitoring of growth mechanisms of hard metal nanocrystals [ 39 , 40 , 41 , 42 , 43 ], in situ (online), high-throughput protein structure screening and analysis during crystallization processes and under various conditions [ 44 , 45 ], real-time monitoring of structural dynamic events during the generation of nano-self-assemblies [ 5 , 28 , 30 , 31 , 46 , 47 ], and online self-assembly behavior of amphiphiles or macromolecules under flow conditions [ 44 , 46 , 48 , 49 , 50 , 51 ]. Further, the use is extended to other research areas, including in situ characterization studies for monitoring the dynamic structural events during the digestion of drug formulations [ 52 ], the exposure of charged nano-self assemblies to divalent ions [ 53 , 54 ], the spinning process of artificial fibers [ 55 ], the generation of single domain supercrystals [ 56 ], the precipitation of crystals in moving droplets [ 57 ], and the nanoparticle agglomeration [ 58 ].…”

Section: Introductionmentioning

confidence: 99%

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Microfluidic Nanomaterial Synthesis and In Situ SAXS, WAXS, or SANS Characterization: Manipulation of Size Characteristics and Online Elucidation of Dynamic Structural Transitions

Yaghmur

Hamad

2022

Molecules

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With the ability to cross biological barriers, encapsulate and efficiently deliver drugs and nucleic acid therapeutics, and protect the loaded cargos from degradation, different soft polymer and lipid nanoparticles (including liposomes, cubosomes, and hexosomes) have received considerable interest in the last three decades as versatile platforms for drug delivery applications and for the design of vaccines. Hard nanocrystals (including gold nanoparticles and quantum dots) are also attractive for use in various biomedical applications. Here, microfluidics provides unique opportunities for the continuous synthesis of these hard and soft nanomaterials with controllable shapes and sizes, and their in situ characterization through manipulation of the flow conditions and coupling to synchrotron small-angle X-ray (SAXS), wide-angle scattering (WAXS), or neutron (SANS) scattering techniques, respectively. Two-dimensional (2D) and three-dimensional (3D) microfluidic devices are attractive not only for the continuous production of monodispersed nanomaterials, but also for improving our understanding of the involved nucleation and growth mechanisms during the formation of hard nanocrystals under confined geometry conditions. They allow further gaining insight into the involved dynamic structural transitions, mechanisms, and kinetics during the generation of self-assembled nanostructures (including drug nanocarriers) at different reaction times (ranging from fractions of seconds to minutes). This review provides an overview of recently developed 2D and 3D microfluidic platforms for the continuous production of nanomaterials, and their simultaneous use in in situ characterization investigations through coupling to nanostructural characterization techniques (e.g., SAXS, WAXS, and SANS).

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Section: Continuous Production and In Situ Characterization Of Nano-s...mentioning

confidence: 99%

Section: Continuous Production and In Situ Characterization Of Nano-s...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microfluidic Nanomaterial Synthesis and In Situ SAXS, WAXS, or SANS Characterization: Manipulation of Size Characteristics and Online Elucidation of Dynamic Structural Transitions

Yaghmur

Hamad

2022

Molecules

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“…Nonetheless, for completeness, we estimate that our proof-of-concept chips cost~$2 per chip excluding the initial fabrication of the mould. For cheaper mass manufacturing, COC or PMMA could be used; for better chemical resistance, whole-Teflon chips 19 or glass microfluidic chips 52 with Viton ® membranes can be used 53 .…”

Section: Microfluidic Chipmentioning

confidence: 99%

Thermally-actuated microfluidic membrane valve for point-of-care applications

Şeşen

Rowlands²

2021

Microsyst Nanoeng

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Microfluidics has enabled low volume biochemistry reactions to be carried out at the point-of-care. A key component in microfluidics is the microfluidic valve. Microfluidic valves are not only useful for directing flow at intersections but also allow mixtures/dilutions to be tuned real-time and even provide peristaltic pumping capabilities. In the transition from chip-in-a-lab to lab-on-a-chip, it is essential to ensure that microfluidic valves are designed to require less peripheral equipment and that they are transportable. In this paper, a thermally-actuated microfluidic valve is presented. The valve itself is fabricated with off-the-shelf components without the need for sophisticated cleanroom techniques. It is shown that multiple valves can be controlled and operated via a power supply and an Arduino microcontroller; an important step towards transportable microfluidic devices capable of carrying out analytical assays at the point-of-care. It is been calculated that a single actuator costs less than $1, this highlights the potential of the presented valve for scaling out. The valve operation is demonstrated by adjusting the ratio of a water/dye mixture in a continuous flow microfluidic chip with Y-junction channel geometry. The power required to operate one microfluidic valve has been characterised both theoretically and experimentally. Cyclical operation of the valve has been demonstrated for 65 h with 585 actuations. The presented valve is capable of actuating rectangular microfluidic channels of 500 μm × 50 μm with an expected temperature increase of up to 5 °C. The fastest actuation times achieved were 2 s for valve closing (heating) and 9 s for valve opening (cooling).

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“…Laboratory-based X-ray diffraction instruments are typically limited to a single wavelength (often copper-Kα, λ = 1.541 Å), whereas it is usually possible to scan a range of wavelengths precisely at synchrotron sources to move diffraction peaks into a detectable range or to allow the X-rays to penetrate through sample environment walls (e.g. scattering through microfluidic chips) [ 11 ]. The extremely high flux of synchrotron sources [ 12 ] also confers a major advantage over even the best lab instrumentation.…”

Section: Introductionmentioning

confidence: 99%

The influence of lipid digestion on the fate of orally administered drug delivery vehicles

Boyd

2021

Biochemical Society Transactions

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This review will focus on orally administered lipid-based drug delivery vehicles and specifically the influence of lipid digestion on the structure of the carrier lipids and their entrained drug cargoes. Digestion of the formulation lipids, which are typically apolar triglycerides, generates amphiphilic monoglycerides and fatty acids that can self-assemble into a diverse array of liquid crystalline structures. Tracking the dynamic changes in self-assembly of the lipid digestion products during digestion has recently been made possible using synchrotron-based small angle X-ray scattering. The influence of lipid chain length and degree of unsaturation on the resulting lipid structuring will be described in the context of the critical packing parameter theory. The chemical and structural transformation of the formulation lipids can also have a dramatic impact on the physical state of drugs co-administered with the formulation. It is often assumed that the best strategy for drug development is to maximise drug solubility in the undigested formulation lipids and to incorporate additives to maintain drug solubility during digestion. However, it is possible to improve drug absorption using lipid digestion in cases where the solubility of the dosed drug or one of its polymorphic forms is greater in the digested lipids. Three different fates for drugs administered with digestible lipid-based formulations will be discussed: (1) where the drug is more soluble in the undigested formulation lipids; (2) where the drug undergoes a polymorphic transformation during lipid digestion; and (3) where the drug is more soluble in the digested formulation lipids.

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Comparison of bulk and microfluidic methods to monitor the phase behaviour of nanoparticles during digestion of lipid-based drug formulations using in situ X-ray scattering

Abstract: Microfluidics affords more control over transformations than current setups to monitor the digestion of lipid-based formulations with X-ray scattering techniques.

Cited by 13 publications

References 37 publications

Microfluidic Nanomaterial Synthesis and In Situ SAXS, WAXS, or SANS Characterization: Manipulation of Size Characteristics and Online Elucidation of Dynamic Structural Transitions

Microfluidic Nanomaterial Synthesis and In Situ SAXS, WAXS, or SANS Characterization: Manipulation of Size Characteristics and Online Elucidation of Dynamic Structural Transitions

Thermally-actuated microfluidic membrane valve for point-of-care applications

The influence of lipid digestion on the fate of orally administered drug delivery vehicles

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