Analysis of the structure of nanocomposites of triglyceride platelets and DNA

Schmiele, Martin; Knittel, Charlotte; Unruh, Tobias; Büsch, Sebastian; Morhenn, Humphrey; Boesecke, Peter; Funari, Sérgio S.; Schweins, Ralf; Lindner, Peter; Westermann, Martin; Steiniger, Frank

doi:10.1039/c5cp01241d

Cited by 7 publications

(3 citation statements)

References 41 publications

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“…The first sample is an aqueous suspension of platelet-shaped tripalmitin nanocrystals (TP NCs). Corresponding systems of TP NCs have been intensively studied by our group (Schmiele et al, 2015;Schmiele, Gehrer et al, 2014) as potential drug delivery systems. The second sample is an aqueous dispersion of commercial silica particles (Ludox TM50, 50 wt%) purchased from Sigma-Aldrich; the average diameter of the SiO 2 NPs is about 26 AE 2 nm (see fitting results in Fig.…”

Section: Performance Evaluation Of the Portable Saxs Systemmentioning

confidence: 99%

A novel experimental approach for nanostructure analysis: simultaneous small-angle X-ray and neutron scattering

et al. 2020

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Exploiting small-angle X-ray and neutron scattering (SAXS/SANS) on the same sample volume at the same time provides complementary nanoscale structural information in two different contrast situations. Unlike an independent experimental approach, the truly combined SAXS/SANS experimental approach ensures the exactness of the probed samples, particularly for in situ studies. Here, an advanced portable SAXS system that is dimensionally suitable for installation in the D22 zone of ILL is introduced. The SAXS apparatus is based on a Rigaku switchable copper/molybdenum microfocus rotating-anode X-ray generator and a DECTRIS detector with a changeable sample-to-detector distance of up to 1.6 m in a vacuum chamber. A case study is presented to demonstrate the uniqueness of the newly established method. Temporal structural rearrangements of both the organic stabilizing agent and organically capped gold colloidal particles during gold nanoparticle growth are simultaneously probed, enabling the immediate acquisition of correlated structural information. The new nano-analytical method will open the way for real-time investigations of a wide range of innovative nanomaterials and will enable comprehensive in situ studies on biological systems. The potential development of a fully automated SAXS/SANS system with a common control environment and additional sample environments, permitting a continual and efficient operation of the system by ILL users, is also introduced. research papers J. Appl. Cryst. (2020). 53, 722-733 Ezzeldin Metwalli et al. Simultaneous SAXS/SANS 723

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Section: Performance Evaluation Of the Portable Saxs Systemmentioning

confidence: 99%

A novel experimental approach for nanostructure analysis: simultaneous small-angle X-ray and neutron scattering

et al. 2020

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“…Submicron-sized solid lipid particles have been proposed for parenteral drug delivery carrier systems by Westesen and Siekmann in 1992. , Detailed studies of the properties of such first generation solid lipid nanoparticles (SLNs) with their complex mesoscopic (length scale between ∼1 nm and some microns) structure have been published subsequently (cf., e.g., refs − ). It has been found that the maximum uptake for drugs by the SLNs is very limited in general due to their essentially crystalline nature. , Nanostructured lipid carriers (NLCs) are still solid nanoparticles but their core consists of a mixture of solid and liquid lipids .…”

Section: Introductionmentioning

confidence: 99%

Mesoscopic Structure of Lipid Nanoparticle Formulations for mRNA Drug Delivery: Comirnaty and Drug-Free Dispersions

Unruh,

Götz,

Vogel

et al. 2024

ACS Nano

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Lipid nanoparticles (LNPs) produced by antisolvent precipitation (ASP) are used in formulations for mRNA drug delivery. The mesoscopic structure of such complex multicomponent and polydisperse nanoparticulate systems is most relevant for their drug delivery properties, medical efficiency, shelf life, and possible side effects. However, the knowledge on the structural details of such formulations is very limited. Essentially no such information is publicly available for pharmaceutical dispersions approved by numerous medicine agencies for the use in humans and loaded with mRNA encoding a mimic of the spike protein of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) as, e.g., the Comirnaty formulation (BioNTech/Pfizer). Here, we present a simple preparation method to mimic the Comirnaty drugfree LNPs including a comparison of their structural properties with those of Comirnaty. Strong evidence for the liquid state of the LNPs in both systems is found in contrast to the designation of the LNPs as solid lipid nanoparticles by BioNTech. An exceptionally detailed and reliable structural model for the LNPs i.a. revealing their unexpected narrow size distribution will be presented based on a combined small-angle X-ray scattering and photon correlation spectroscopy (SAXS/PCS) evaluation method. The results from this experimental approach are supported by light microscopy, 1 H NMR spectroscopy, Raman spectroscopy, cryogenic electron microscopy (cryoTEM), and simultaneous SAXS/SANS studies. The presented results do not provide direct insights on particle formation or dispersion stability but should contribute significantly to better understanding the LNP drug delivery process, enhancing their medical benefit, and reducing side effects.

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“…To eventually understand the underlying particle formation and stabilization processes, it is reasonable to first conduct comprehensive structural investigations of final NPs prior to in situ studies. The combination of small-angle X-ray and neutron scattering (SAXS, SANS) studies has been proven to be a powerful tool for the molecular characterization of the stabilizing layer of dispersed organic and inorganic NPs. − For instance, the structures of nanosized lecithin-stabilized tetracosane lipid emulsions and suspensions produced by HPH were extensively investigated by SAXS and SANS. , The thickness of the lecithin layer was found to be 0.16 and 0.105 nm for the emulsion and the suspension, respectively, while no penetration of tetracosane molecules into the stabilizer layer could be observed. Studies on the size, morphology, and bioavailability of NPs prepared by AP exist. , The impact of AP on the molecular structure as well as the particle formation and stabilization process are, however, still not well understood, nor is the achievement of small particle sizes trivial.…”

Section: Introductionmentioning

confidence: 99%

Internal Structure of Nanometer-Sized Droplets Prepared by Antisolvent Precipitation

et al. 2019

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Antisolvent precipitation (AP) is a low-cost and less-invasive preparation alternative for organic nanoparticles compared to top-down methods such as high-pressure homogenization or milling. Here we report on particularly small organic nanoparticles (NPs) prepared by AP. It has been found for various materials that these NPs in their liquid state exhibit a significant degree of molecular order at their interface toward the dispersion medium including ubiquinones (coenzyme Q10), triglycerides (trimyristin, tripalmitin), and alkanes (tetracosane). This finding is independent of the use of a stabilizer in the formulation. While this is obviously a quite general interfacial structuring effect, the respective structural details of specific NPs systems might differ. Here, a detailed structural characterization of very small liquid coenzyme Q10 (Q10) NPs is presented as a particular example for this phenomenon. The Q10 NPs have been prepared by AP in the presence of two different stabilizers, sodium dodecyl sulfate (SDS) and pentaethylene glycol monododecyl ether (C12E5), respectively, and without any stabilizer. The NPs’ size is initially analyzed by photon correlation spectroscopy (PCS). The SDS-stabilized Q10 NPs have been studied further by differential scanning calorimetry (DSC), small-angle X-ray and neutron scattering (SAXS, SANS), wide-angle X-ray scattering (WAXS), and cryogenic transmission electron microscopy (CryoTEM). A simultaneous analysis of SAXS and contrast variation SANS studies revealed the molecular arrangement within the interface between the NPs and the dispersion medium. The Q10 NPs stabilized by SDS and C12E5, respectively, are small (down to 19.9 nm) and stable (for at least 16 months) even when no stabilizer is used. The SDS-stabilized Q10 NPs reported here, are therewith, to the best of our knowledge, the smallest organic NPs which have been reported to be prepared by AP so far. In particular, these NPs exhibit a core–shell structure consisting of an amorphous Q10 core and a surrounding shell, which is mainly composed of oriented Q10 molecules and aligned SDS molecules. This structure suggests a significant amphiphilic behavior and a rather unexpected stabilizing role of Q10 molecules.

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Analysis of the structure of nanocomposites of triglyceride platelets and DNA

Cited by 7 publications

References 41 publications

A novel experimental approach for nanostructure analysis: simultaneous small-angle X-ray and neutron scattering

A novel experimental approach for nanostructure analysis: simultaneous small-angle X-ray and neutron scattering

Mesoscopic Structure of Lipid Nanoparticle Formulations for mRNA Drug Delivery: Comirnaty and Drug-Free Dispersions

Internal Structure of Nanometer-Sized Droplets Prepared by Antisolvent Precipitation

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