The estimated cost of getting a new medicine to market is now in excess of $2.6 billion, with an additional $300 million (approx.) typically being directed towards post market approval research and development activities (including testing of new indications, new formulations and new dosage strengths and regimens) (Nature Reviews Drug Discovery 13, 877 (2014)). These costs have increased >145% since 2003, and reflect an increasingly complex process in which there remains a high chance of failure in the expensive later phases of development. With the aim of reducing the times and costs associated with medicine development, increasing attention has focused on the development of approaches to better predict and/or optimize the behaviour of actives and their formulations at an earlier stage of development. Recent research within the School of Pharmacy (University of Nottingham (UoN)) has focussed on the application of advanced surface analytical and biophysical tools to address this need. This proposal will build on this activity via an intersectoral researcher exchange program focussed on supporting future pharmaceutical formulations development. The principal objective of FutForm is to translate the advanced analytical approaches developed within UoN, so that they become embedded into industrial practice for the development of future pharmaceutical processes and therapies. This will be achieved through a collaborative programme of researcher secondments with three small-medium enterprise (SME) companies, each with early stage innovative technologies in areas of importance to the future pharmaceutical industry, namely; enzyme formulations for improved cell isolation (Abiel s.r.l; Italy), nanoparticle platform formulations for oral and topical drug delivery (Inovapotek, Pharmaceutical Research and Development Lda; Portugal) and hydrogel formulations for cell-delivery (Hy2Care b.v.; Netherlands).

The European Union (EU) Revised Renewable Energy Directive 2023/2413/EU states the need of advancing renewable energy sources to meet the commitments of the Paris Agreement while keeping the EU a global leader in renewables. Among the existing renewable energy technologies, photovoltaics are one of the most mature, promising to reach a worldwide production of 8,519 GW by 2050. Silicon-PVs (Si-PVs) are the most advanced approach to reach the above goal at low costs. However, they still face the problem of thermalization, an energy loss mechanism by which the excess energy of the absorbed photons with respect to the Si band gap is lost. BioSinFin will tackle this issue developing the first bioinspired photomultiplier coating based on singlet fission, a multiple exciton generation process. Here, singlet-fission active chromophores and red-emitting materials are bioconjugated to protein scaffolds with nm precision and used to fabricate a coating to sensitize Si solar cells promising up to an additional 5% to the absolute power conversion efficiency of commercial Si PVs (i.e. about 25% improvement) using a low-cost and sustainable coating, leading a revalue of Si-PV market of up to 15%. This multi-photon protein family and its respective coatings will allow to realize a low-cost, sustainable, environmentally friendly, and highly performing new generation of multi-photon low-energy bio-hybrid emitters of great interest for photonics with a final proof on overcoming thermalization in silicon solar cells, helping the EU to fulfil the Revised Renewable Energy Directive.

The EU priority action lines state the need of advancing white light-emitting diodes (WLED) replacing color filters with inorganic phosphors (IP: rare-earth elements and Cd quantum dot) for non-toxic and sustainable organic phosphors (OP). ENABLED is inspired by highly efficient Bio-WLEDs based on fluorescent proteins (FPs), which are stable over weeks and beyond the state-of-the-art OP-WLEDs. However, the stability is limited by the intrinsic photodeactivation of FPs since natural chromophores were not matured by Nature to stand high photon flux excitations. Thus, there is an imperative need to enforce the evolution of photostable FPs directly prepared in bacteria. ENABLED proposes a radically new approach to prepare low-cost, highly efficient, and stable Bio-WLEDs by developing new biological synthesis tools to produce novel artificial fluorescent proteins (AFPs) in bacteria, which will be achieved by combining tailored natural as well as de novo protein scaffolds with synthetic LED emitters (PLQY>50% with high photostabilities). Thus, the novel Bio-WLEDs will also overcome previous limitations connected to photo-deactivation of natural chromophores. ENABLED aims to reach TRL4 for both AFP synthesis and Bio-WLEDs to fully meet the lighting needs at the forefront of the EU technology scenario by the end of the project.

Diabetes mellitus is a chronic disease characterised by high blood glucose due to inadequate insulin production and/or insulin resistance which affects 382 million people worldwide. Pancreatic islet transplantation is an extremely promising cure for insulin-sensitive diabetes mellitus (ISDM), but side effects of lifelong systemic immunosuppressive therapy, short supply of donor islets and their poor survival and efficacy in the portal vein limit the application of the current clinical procedure to the most at-risk brittle Type I diabetes (T1D) sufferers. The DRIVE consortium will develop a novel suite of bio-interactive hydrogels (β-Gel) and on-demand drug release systems to deliver islets in a protective macrocapsule (β-Shell) to the peritoneum with targeted deposition using a specialised injection catheter (β-Cath). Pancreatic islets will be microencapsulated in β-Gels; biofunctionalised injectable hydrogels containing immunosuppressive agents and polymeric microparticles with tuneable degradation profiles for localised delivery of efficacy cues. These β-Gels will be housed in a porous retrievable macrocapsule, β-Shell, for added retention, engraftment, oxygenation, vascularisation and immunoprotection of the islets. A minimally invasive laparoscopic procedure (O-Fold) will be used to create an omental fold and at the same time deliver β-Shell. An extended residence time in β-Gel will enhance long-term clinical efficacy of the islets and result in improved glycemic control. The novel β-Gels will also be developed as human three-dimensional in-vitro models of in-vivo behaviour. Islet harvesting and preservation technologies will be developed to facilitate their optimised yield, safe handling and transport, and ease of storage. DRIVE will also enable the future treatment of a broader range of T1 and insulin-sensitive T2 diabetics by working with induced pluripotent stem cell experts to ensure the compatibility of our system with future stem cell sources of β-cells.