Mild synthesis of poly(HEMA)-networks as well-defined nanoparticles in supercritical carbon dioxide

Free-radical dispersion polymerisation of 2-hydroxyethyl methacrylate was carried out in supercritical carbon dioxide (scCO2) in the presence of stabilisers based on polyethylene oxide (PEO) and poly(heptadecafluorodecyl acrylate) (PFDA). Different architectures of copolymers (random, palm-tree and diblock) were tested for their surface tension, cloud point and as a stabilising agent. The diblock architecture was found to be the best candidate resulting in poly(HEMA) spherical particles with a size of 316 nm. Furthermore, the effect of the CO2-phobic block (PEO) in the diblock architecture was investigated by using three different chain lengths (1000, 2000, 5000 g mol−1). By optimizing the stabiliser composition and structure, mild reaction conditions have been identified allowing us to obtain well-defined spherical cross-linked poly(HEMA) particles with a mean diameter of unprecedented low size (216 nm) at a temperature as low as 35 °C

Highly coloured and electrophoretically active polymer microparticles via staggered dispersion polymerisation in supercritical carbon dioxide and dodecane

Devices featuring electrophoretic displays (EPD) have become extremely popular in recent years because of their low power consumption, high readability and thin display designs, but a product with a full colour gamut comparable with liquid crystal displays (LCDs) has not yet been commercialised. In this article, we demonstrate that staggering the addition of methyl methacrylate (MMA) monomer and low quantities of a coloured dye crosslinker is an effective route to producing well-defined and covalently-linked, strongly coloured PMMA microparticles in one-pot, via dispersion polymerisation in supercritical carbon dioxide (scCO2). This novel methodology is synthetically simple, readily scalable and has the added cachet of being cost effective because the functional molecules can be confined on the microparticle surface such that even at low concentrations, the resulting materials are brightly coloured. We then demonstrate the applicability of this approach to another functional comonomer/crosslinker system in 2-dimethylaminoethyl methacrylate (DMAEMA)/ethyleneglycol dimethacrylate (EGDMA), in this case allowing hierarchically structured ‘pomegranate-like’ microparticles with polarisable charge to be produced over a range of DMAEMA loadings as high as 44 wt%. Finally, the performance of these materials in out-of-plane EPD test cells is compared against analogues synthesised in dodecane. These tests revealed that the coloured microparticles fabricated in scCO2 performed as well as or better than their dodecane synthesised counterparts, consistently producing the cleanest white state and achieving effective colour switching over ten cycles

The use of shift reagents in ion mobility-mass spectrometry: studies on the complexation of an active pharmaceutical ingredient with polyethylene glycol excipients

Gas-phase ion mobility studies of mixtures containing polyethylene glycols (PEG) and an active pharmaceutical ingredient (API), Lamivudine, have been carried out using electrospray ionization-ion mobility spectrometry-quadrupole-time-of-flight mass spectrometry (ESI-IMS-Q-TOF). In addition to protonated and cationised PEG oligomers, a series of high molecular weight ions were observed and identified as non-covalent complexes formed between Lamivudine and PEG oligomers. The non-covalent complex ions were dissociated using collision induced dissociation (CID) after separation in the ion mobility drift tube to recover the protonated Lamivudine free from interfering matrix ions and with a drift time associated with the precursor complex. The potential of PEG excipients to act as ‘shift reagents’, which enhance selectivity by moving the mass/mobility locus to an area of the spectrum away from interferences, is demonstrated for the analysis of Lamivudine in a Combivir formulation containing PEG and Lamivudine

How does dense phase CO2 influence the phase behaviour of block copolymers synthesised by dispersion polymerisation?

Block copolymers synthesised in supercritical CO2 dispersion undergo in situ self-assembly which can result in a range of nanostructured microparticles. However, our previous study revealed that copolymers with different block combinations possessed different microphase separated morphologies at identical block volume fractions. In this paper, we follow up those initial observations. By examining the phase behaviour of a selection of structurally diverse block copolymers, we explore the structural factors which influence the conflicting self-assembly behaviours. The composition dependence of the morphology is found to be strongly related to the CO2-philicity of the second block relative to poly(methyl methacrylate) (PMMA). Whilst PMMA-b-poly(benzyl methacrylate) (PBzMA) and PMMA-b-poly(N,N-dimethylaminoethylmethacrylate) (PDMAEMA) phase behaviour follows traditional diblock copolymer phase diagrams, PMMA-b-poly(styrene) (PS) and PMMA-b-poly(4-vinyl pyridine) (P4VP), which comprise blocks with the greatest contrast in CO2-philicity, self-assemble into unexpected morphologies at several different block volume fractions. The morphology of these copolymers in the microparticulate form was found to revert to the predicted equilibrium morphology when the microparticles were re-cast as films and thermally annealed. These findings provide strong evidence that CO2 acts as a block-selective solvent during synthesis. The CO2-selectivity was exploited to fabricate various kinetically trapped non-lamellar morphologies in symmetrical PMMA-b-PS copolymers by tuning the ratio of polymer:CO2. Our data demonstrate that CO2 can be exploited as a facile process modification to control the self-assembly of block copolymers within particles

Starch/Poly(glycerol-adipate) Nanocomposites: A Novel Oral Drug Delivery Device

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Biocompatible and bio-based materials are an appealing resource for the pharmaceutical industry. Poly(glycerol-adipate) (PGA) is a biocompatible and biodegradable polymer that can be used to produce self-assembled nanoparticles (NPs) able to encapsulate active ingredients, with encouraging perspectives for drug delivery purposes. Starch is a versatile, inexpensive, and abundant polysaccharide that can be effectively applied as a bio-scaffold for other molecules in order to enrich it with new appealing properties. In this work, the combination of PGA NPs and starch films proved to be a suitable biopolymeric matrix carrier for the controlled release preparation of hydrophobic drugs. Dynamic Light Scattering (DLS) was used to determine the size of drug-loaded PGA NPs, while the improvement of the apparent drug water solubility was assessed by UV-vis spectroscopy. In vitro biological assays were performed against cancer cell lines and bacteria strains to confirm that drug-loaded PGA NPs maintained the effective activity of the therapeutic agents. Dye-conjugated PGA was then exploited to track the NP release profile during the starch/PGA nanocomposite film digestion, which was assessed using digestion models mimicking physiological conditions. The collected data provide a clear indication of the suitability of our biodegradable carrier system for oral drug delivery.Peer reviewedFinal Published versio

Photoproduction of π0\pi^0-pairs off protons and off neutrons

Total cross sections, angular distributions, and invariant-mass distributions have been measured for the photoproduction of $\pi^0\pi^0$ pairs off free protons and off nucleons bound in the deuteron. The experiments were performed at the MAMI accelerator facility in Mainz using the Glasgow photon tagging spectrometer and the Crystal Ball/TAPS detector. The accelerator delivered electron beams of 1508 and 1557~MeV, which produced bremsstrahlung in thin radiator foils. The tagged photon beam covered energies up to 1400~MeV. The data from the free proton target are in good agreement with previous measurements and were only used to test the analysis procedures. The results for differential cross sections (angular distributions and invariant-mass distributions) for free and quasi-free protons are almost identical in shape, but differ in absolute magnitude up to 15\%. Thus, moderate final-state interaction effects are present. The data for quasi-free neutrons are similar to the proton data in the second resonance region (final state invariant masses up to $\approx$1550~MeV), where both reactions are dominated by the $N(1520)3/2^-\rightarrow \Delta(1232)3/2^+\pi$ decay. At higher energies, angular and invariant-mass distributions are different. A simple analysis of the shapes of the invariant-mass distributions in the third resonance region is consistent with strong contributions of an $N^{\star}\rightarrow N\sigma$ decay for the proton, while the reaction is dominated by a sequential decay via a $\Delta\pi$ intermediate state for the neutron. The data are compared to predictions from the Two-Pion-MAID model and the Bonn-Gatchina coupled channel analysis.Comment: accepted for publication in Eur. Phys. J.

Photoproduction of π0-pairs off protons and off neutrons

Total cross sections, angular distributions, and invariant-mass distributions have been measured for the photoproduction of π0π0 pairs off free protons and off nucleons bound in the deuteron. The experiments were performed at the MAMI accelerator facility in Mainz using the Glasgow photon tagging spectrometer and the Crystal Ball/TAPS detector. The accelerator delivered electron beams of 1508 and 1557MeV, which produced bremsstrahlung in thin radiator foils. The tagged photon beam covered energies up to 1400MeV. The data from the free proton target are in good agreement with previous measurements and were only used to test the analysis procedures. The results for differential cross sections (angular distributions and invariant-mass distributions) for free and quasi-free protons are almost identical in shape, but differ in absolute magnitude up to 15%. Thus, moderate final-state interaction effects are present. The data for quasi-free neutrons are similar to the proton data in the second resonance region (final-state invariant masses up to ≈1550 MeV), where both reactions are dominated by the N(1520)3/2−→Δ(1232)3/2+π decay. At higher energies, angular and invariant-mass distributions are different. A simple analysis of the shapes of the invariant-mass distributions in the third resonance region is consistent with strong contributions of an N⋆→Nσ decay for the proton, while the reaction is dominated by a sequential decay via a Δπ intermediate state for the neutron. The data are compared to predictions from the Two-Pion-MAID model and the Bonn-Gatchina coupled-channel analysis

Measurement of the transverse target and beam-target asymmetries in η\eta meson photoproduction at MAMI

We present new data for the transverse target asymmetry T and the very first data for the beam-target asymmetry F in the $\vec \gamma \vec p\to\eta p$ reaction up to a center-of-mass energy of W=1.9 GeV. The data were obtained with the Crystal-Ball/TAPS detector setup at the Glasgow tagged photon facility of the Mainz Microtron MAMI. All existing model predictions fail to reproduce the new data indicating a significant impact on our understanding of the underlying dynamics of $\eta$ meson photoproduction. The peculiar nodal structure observed in existing T data close to threshold is not confirmed.Comment: 5 pages, 3 figures, accepted for publication in PR

Photoproduction of pi0-mesons off neutrons in the nucleon resonance region

Precise angular distributions have been measured for the first time for the photoproduction of $\pi^{0}$-mesons off neutrons bound in the deuteron. The effects from nuclear Fermi motion have been eliminated by a complete kinematic reconstruction of the final state. The influence of final-state-interaction effects has been estimated by a comparison of the reaction cross section for quasi-free protons bound in the deuteron to the results for free protons and then applied as a correction to the quasi-free neutron data. The experiment was performed at the tagged photon facility of the Mainz Microtron MAMI with the Crystal Ball and TAPS detector setup for incident photon energies between $0.45$~GeV and $1.4$~GeV. The results are compared to the predictions from reaction models and partial-wave analyses based on data from other isospin channels. The model predictions show large discrepancies among each other and the present data will provide much tighter constraints. This is demonstrated by the results of a new analysis in the framework of the Bonn-Gatchina coupled-channel analysis which included the present data.Comment: accepted for publication in Phys; Rev. Let

The isospin structure of photoproduction of pi-eta pairs from the nucleon in the threshold region

Photoproduction of $\pi\eta$-pairs from nucleons has been investigated from threshold up to incident photon energies of $\approx$~1.4~GeV. The quasi-free reactions $\gamma p\rightarrow p\pi^0\eta$, $\gamma n\rightarrow n\pi^0\eta$, $\gamma p\rightarrow n\pi^+\eta$, and $\gamma n\rightarrow p\pi^-\eta$ were for the first time measured from nucleons bound in the deuteron. The corresponding reactions from a free-proton target were also studied to investigate final-state interaction effects (for neutral pions the free-proton results could be compared to previous measurements; the $\gamma p\rightarrow n\pi^+\eta$ reaction was measured for the first time). For the $\pi^0\eta$ final state coherent production via the $\gamma d\rightarrow d\pi^0\eta$ reaction was also investigated. The experiments were performed at the tagged photon beam of the Mainz MAMI accelerator using an almost $4\pi$ coverage electromagnetic calorimeter composed of the Crystal Ball and TAPS detectors. The total cross sections for the four different final states obey the relation $\sigma(p\pi^0\eta)$ $\approx$ $\sigma(n\pi^0\eta)$ $\approx$ $2\sigma(p\pi^-\eta)$ $\approx$ $2\sigma(n\pi^+\eta)$ as expected for a dominant contribution from a $\Delta^{\star}\rightarrow\eta\Delta(1232)\rightarrow\pi\eta N$ reaction chain, which is also supported by the shapes of the invariant-mass distributions of nucleon-meson and $\pi$-$\eta$ pairs. The experimental results are compared to the predictions from an isobar reaction model.Comment: accepted for publication in Phys. Lett.