Emmet J. O'Reilly

The application of water soluble, mega-Stokes-shifted BODIPY fluorophores to cell and tissue imaging.

BODIPY (4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene) fluorophores are widely used in bioimaging to label proteins, lipids and nucleotides, but in spite of their attractive optical properties they tend to be prone to self‐quenching because of their notably small Stokes shift. Herein, we compare two BODIPY compounds from a recently developed family of naphthyridine substituted BODIPY derivatives, one a visible emitting derivative (BODIPY‐VIS) and one a near‐infrared emitting fluorophore with a Stokes shift of approximately 165 nm as contrast reagents for live mammalian cells and murine brain tissue. The compounds were rendered water soluble by their conjugation to polyethylene glycol (PEG). Both PEGylated compounds exhibited good cell uptake compared with their parent compounds and confocal fluorescence microscopy revealed all dyes explored to be nuclear excluding, localizing predominantly within the lipophilic organelles; the endoplasmic reticulum and mitochondria. Cytotoxicity studies revealed that these BODIPY derivatives are modestly cytotoxic at concentrations exceeding 10 μM where they induce apoptosis and necrosis. Although the quantum yield of emission of the visible emitting fluorophore was over an order of magnitude greater than the Mega‐Stokes shifted probe, the latter showed considerably reduced tendency to self quench and less interference from autofluorescence. The near‐infrared probe also showed good penetrability and staining in live tissue samples. In the latter case similar tendency to exclude the nucleus and to localize in the mitochondria and endoplasmic reticulum was observed as in live cells. This to our knowledge is the first demonstration of such a Mega‐Stokes BODIPY probe applied to cell and tissue imaging.

Electrochemiluminescence platform for the detection of C-reactive proteins: application of recombinant antibody technology to cardiac biomarker detection

This work exploits the high-affinity of recombinant antibodies and low background electrochemiluminescence (ECL) for cardiac-biomarker detection. The developed assay is capable of fg mL−1 detection limits as well as the detection of C-Reactive Protein (CRP) over a clinically relevant range. The assay demonstrated robust reproducibility, selectivity and stability while also highlighting a novel platform for detection of cardiac biomarkers at low concentrations.

Spray drying ternary amorphous solid dispersions of ibuprofen – An investigation into critical formulation and processing parameters

HIGHLIGHTSSystematic Design of Experiment (DoE) approach.Simultaneous analysis of the effect of process and formulation factors.Studying molecular level interactions via FTIR and SSNMR analyses. ABSTRACT A design of experiment (DoE) approach was used to investigate the critical formulation and processing parameters in spray drying ternary amorphous solid dispersions (ASDs) of ibuprofen. A range of 16 formulations of ibuprofen, HPMCP‐HP55 and Kollidon VA 64 were spray dried. Statistical analysis revealed the interrelation of various spray drying process conditions and formulation factors, namely solution feed rate, inlet temperature, Active Pharmaceutical Ingredient (API)/excipients ratio and dichloromethane (DCM)/methanol (MeOH) ratio. Powder X‐ray diffraction analysis (PXRD) showed that all the samples with the lowest API/excipient ratio (1:4) were amorphous, while others were crystalline. Moreover, differential scanning calorimetry (DSC) analysis was employed to investigate ASD formulation more in‐depth. The glass transition temperatures (Tg) of all ASDs were in the range 70–79 °C, while crystalline formulations displayed an endothermic peak of melting of crystalline ibuprofen in the range of 50–80 °C. The high Tg of ASDs was an indication of highly stable ASD formulations as verified via PXRD at zero day and afterward at 1, 1.5, 3 and 6 month intervals. The intermolecular interactions between ibuprofen molecule and excipients were studied by Fourier transform infrared spectroscopy (FTIR) and solid‐state nuclear magnetic resonance (ssNMR) spectroscopy. FTIR and Carbon‐13 ssNMR analysis indicated that hydrogen bond formation involving the carboxyl group in ibuprofen within the ASDs is likely. More importantly, the solubility of ibuprofen in ASD formulations is improved compared to pure ibuprofen. This was due to both the amorphous structure of ibuprofen and of the existence of amphiphilic excipient, Kollidon VA 64, in the formulation.

Solid State Photochemistry of Novel Composites Containing Luminescent Metal Centers and Poly(2-methoxyaniline-5-sulfonic acid)

Steady state luminescence and measurements of the luminescent lifetime as well as cyclic voltammetry have been used to elucidate the mechanism and dynamics of interaction between a luminescent ruthenium metal center and two different fractions of poly(2-methoxyaniline-5-sulfonic acid) (PMAS). The two fractions, high molecular weight (HMWT) PMAS and low molecular weight (LMWT) PMAS oligomer, showed significantly distinctive influences on the luminophore. The HMWT PMAS, confirmed to be an emeraldine salt by its characteristic redox chemistry, greatly impacted the diffusion coefficient of the Ru2+/3+ within the composite film, increasing the diffusion coefficient, DCT, by 2 orders of magnitude. The HMWT PMAS also resulted in quenching of the ruthenium-based emission. Significantly, these results indicate that quenching involves both static and dynamic processes, with the static quenching being the dominant process, suggesting that the metal center and polymer backbone were strongly associated. In stark contrast, the LMWT PMAS did not influence the electrochemical properties of the ruthenium metal center; however, it did double the emission observed from the ruthenium metal center. The insensitivity of the luminescence lifetime does suggest that, as with the HMWT PMAS, LWMT PMAS is strongly associated with the ruthenium metal center. The enhanced luminescence may allow for many potential sensor developments based on the luminescent ruthenium metal center, while the HMWT PMAS quenching could be utilized within quenching-based strategies or electrochemical devices.

Formation of reworkable nanocomposite adhesives by dielectric heating of epoxy resin embedded Fe3O4 hollow spheres

Epoxy resin (ER) thermosetting adhesives provide highly cross-linked 3-dimensional structures leading to highly stable and strong mechanical/physical performance in a wide range of bonding applications. However, such excellent physical attributes pose a significant challenge with respect to disassembly of the bonded adherends and previous disassembly methods have resulted in damage to the adherends. Hence, this paper presents a specifically engineered re-workable nanocomposite adhesive, created by embedding dielectric sensitive Fe3O4 hollow nanospheres (HNSs) in epoxy resin. This nanocomposite adhesive can be completely degraded by dielectric heating, resulting in facile disassembly of bonded adherends. FESEM and 3D Micro-CT characterisation demonstrates good dispersibility of the HNSs in cured ER, while the dielectric degradation performance and hardness/modulus were investigated by FESEM and nanoindentation. Results show that the Fe3O4 HNSs can effectively convert the microwave energy into thermal energy to significantly degrade the mechanical properties of the adhesive modulus and hardness by 83.4% and 90%, respectively. FESEM and HRTEM imaging attributes the reduction in nanocomposite adhesive properties to the formation of spatial voids nucleating from the embedded nanomaterials. Prior to dielectric heating, tensile loaded single lap-shear bonded joint tests indicated that the nanocomposite adhesive was 19.3% stronger than its neat ER adhesive counterpart due a nano-reinforcement toughening mechanism. However, after 3 minutes of dielectric heating exposure, the nanocomposite adhesive joint strength was reduced by 96.3% compared to just 18.7% for the neat ER adhesive, demonstrating the excellent re-workable performance of our new nanocomposite adhesive.

Temperature controlled shape evolution of iron oxide nanostructures in HMTA media

This work reported an improved approach to the synthesis of iron oxide nanostructures using iron(III) chloride as the precursor and hexamethylenetetramine (HMTA) as the key auxiliary. A range of iron oxide (alkoxide) nanostructures including nanosheets, hierarchical flowers (assembled by thin nanosheets), mesoporous hollow nanospheres and solid nanospheres were obtained only by altering the reaction temperature from 180 °C to 240 °C in a single synthetic protocol. Supplementary experiments driven by reaction time were designed in order to further clarify the morphological evolution behaviors of these nanostructures, which discovered that the spherical morphology with the size of about 150–200 nm formed from the inside of micro-scaled flower-like clusters gradually by the condensing and weaving of curled nanosheets, suggesting that the hollow nanospheres were obtained consequently by the further condensation of incompact nanospheres with the assistance of the rearrangement of surfactant micelles, followed by the oriented attachment assembly and Ostwald ripening.

Electrospun API-loaded mixed matrix membranes for controlled release

The development of biocompatible membrane materials capable of delivering active pharmaceutical ingredients (APIs) over a fixed time period offers significant advantages to the pharmaceutical and biomedical industries alike. In addition the incorporation of APIs within polymeric materials potentially allows for the formation of amorphous solid dispersions (ASDs), which have shown enhanced bioavailability, increased dissolution profiles and enhanced adsorption into the blood stream. Mixed matrix membranes (MMMs) have been at the forefront of such developments, however manufacturing MMMs with consistent batch to batch physical characteristics has proved challenging thereby significantly impeding the use of such materials by the pharmaceutical sector. This article describes the development, for the first time, of API and molecular sieve loaded mixed matrix membranes (MMMs) via electrospinning techniques. The developed membranes displayed consistent and controllable physical properties and more efficient API release relative to membranes prepared using traditional casting techniques. Mathematical modelling disclosed that the membranes generated via electrospinning show excellent correlation between experimental and predicted API release kinetics thereby paving the way for the development of MMMs for both pharmaceutical and biomedical applications.