Quantitative monitoring and modelling of retrodialysis drug delivery in a brain phantom.

A vast number of drug molecules are unable to cross the blood-brain barrier, which results in a loss of therapeutic opportunities when these molecules are administered by intravenous infusion. To circumvent the blood-brain barrier, local drug delivery devices have been developed over the past few decades such as reverse microdialysis. Reverse microdialysis (or retrodialysis) offers many advantages, such as a lack of net volume influx to the intracranial cavity and the ability to sample the tumour's micro-environment. However, the translation of this technique to efficient drug delivery has not been systematically studied. In this work, we present an experimental platform to evaluate the performance of microdialysis devices in reverse mode in a brain tissue phantom. The mass of model drug delivered is measured by computing absorbance fields from optical images. Concentration maps are reconstructed using a modern and open-source implementation of the inverse Abel transform. To illustrate our method, we assess the capability of a commercial probe in delivering methylene blue to a gel phantom. We find that the delivery rate can be described by classical microdialysis theory, except at low dialysate flow rates where it is impacted by gravity, and high flow rates where significant convection to the gel occurs. We also show that the flow rate has an important impact not only on the overall size of the drug plume, but also on its shape. The numerical tools developed for this study have been made freely available to ensure that the method presented can be used to rapidly and inexpensively optimise probe design and protocol parameters before proceeding to more in-depth studies.

Direct-writing microporous polymer architectures - print, capture and release.

In the nature-inspired breath figure method, rafts of condensed water droplets self-organise and imprint into a permanent microporous polymer structure. This could have exciting applications in drug delivery, tissue engineering and sensors but it is extremely difficult to control or functionalise the final structure. Here, we show direct-writing of droplets onto fluid surfaces by inkjet printing as a breakthrough to dial-in a required pattern, structure and function into the polymer film.

Capturing the value in printed pharmaceuticals - A study of inkjet droplets released from a polymer matrix.

The future of personalised combination dosages will rely on the programming and delivery of multiple, separate APIs, their carrier fluids and excipients to a stable matrix, where each will remain separate until it is needed to be released. A recent technique has demonstrated how to print, capture and release materials from a polymer matrix using inkjet printing, a low cost and customisable technique. Droplets of a formulation are delivered to a fluid polymer matrix, where they are imbibed and remain pinned just under the upper surface, held in place by a balance of interfacial energies. Once the surrounding matrix cures and solidifies, the coating or matrix has trapped the formulation, but each drop has a small opening or pore to the outside that will allow delivery through diffusion. However, while the trapping mechanism has been explored in detail, to-date the release involved in this delivery has never been studied or quantified to the same level. Here we show a first study to quantify the release of a model system from a polymer matrix. An aqueous fluorescein solution is delivered and trapped, with release demonstrated to an agarose gel and aqueous environments. The work reveals that the balance of interfacial tensions prevents a reliable release until low concentrations of surfactant are included. This provides a route forward to further explore stabilising combinations of drugs within one material using a digitally controlled and affordable technique.

A single-component photorheological fluid with light-responsive viscosity.

Viscoelastic fluids whose rheological properties are tunable with light have the potential to deliver significant impact in fields relying on a change in flow behavior, such as in-use tuning of combined efficient heat-transfer and drag-reduction agents, microfluidic flow and controlled encapsulation and release. However, simple, single-component systems must be developed to allow integration with these applications. Here, we report a single-component viscoelastic fluid, capable of a dramatic light-sensitive rheological response, from a neutral azobenzene photosurfactant, 4-hexyl-4'butyloxymonotetraethylene glycol (C6AzoOC4E4) in water. From cryo-transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS) and rheology measurements, we observe that the photosurfactant forms an entangled network of wormlike micelles in water, with a high viscosity (28 Pa s) and viscoelastic behaviour. UV irradiation of the surfactant solution creates a less dense micellar network, with some vesicle formation. As a result, the solution viscosity is reduced by four orders of magnitude (to 1.2 × 10-3 Pa s). This process is reversible and the high and low viscosity states can be cycled several times, through alternating UV and blue light irradiation.

Synergistic photoluminescence enhancement in conjugated polymer-di-ureasil organic-inorganic composites.

Poly(fluorene) conjugated polyelectrolyte (CPE)-di-ureasil organic-inorganic composites have been prepared using a versatile sol-gel processing method, which enables selective localisation of the CPE within the di-ureasil matrix. Introduction of the CPE during the sol-gel reaction leads to a homogeneous distribution of the CPE throughout the di-ureasil, whereas a post-synthesis solvent permeation route leads to the formation of a confined layer of the CPE at the di-ureasil surface. The CPE and the di-ureasil both function as photoactive components, contributing directly to, and enhancing the optical properties of their composite material. The bright blue photoluminescence exhibited by CPE-di-ureasils is reminiscent of the parent CPE; however the distinct contribution of the di-ureasil to the steady-state emission profile is also apparent. This is accompanied by a dramatic increase in the photoluminescence quantum yield to >50%, which is a direct consequence of the synergy between the two components. Picosecond time-correlated single photon counting measurements reveal that the di-ureasil effectively isolates the CPE chains, leading to emissive trap sites which have a high radiative probability. Moreover, intimate mixing of the CPE and the di-ureasil, coupled with their strong spectral overlap, results in efficient excitation energy transfer from the di-ureasil to these emissive traps. Given the simple, solution-based fabrication method and the structural tunability of the two components, this approach presents an efficient route to highly desirable CPE-hybrid materials whose optoelectronic properties may be enhanced and tailored for a targeted application.

Cationic polythiophene-surfactant self-assembly complexes: phase transitions, optical response, and sensing.

The absorption and photoluminescence spectra of the cationic conjugated polyelectrolyte poly[3-(6-trimethylammoniumhexyl)thiophene] (P3TMAHT) were observed to be dramatically altered in the presence of anionic surfactants due to self-assembly through ionic complex formation. Small-angle neutron scattering (SANS), UV/vis, and photoluminescence spectroscopy were used to probe the relationship between the supramolecular complex organization and the photophysical response of P3TMAHT in the presence of industrially important anionic surfactants. Subtle differences in the surfactant mole fraction and chemical structure (e.g., chain length, headgroup charge density, perfluorination) result in marked variations in the range and type of complexes formed, which can be directly correlated to a unique colorimetric and fluorimetric fingerprint. Our results show that P3TMAHT has potential as an optical sensor for anionic surfactants capable of selectively identifying distinct structural subgroups through dual mode detection.