Following oral administration, the bioavailability of progestogens is very low and highly variable, in part due to metabolism by cytochrome P450 enzymes found in the mucosa of the small intestine. Conversely, the mucosa in the colon contains much lower levels of cytochrome P450 enzymes, thus, colonic delivery of progestogens may be beneficial. Microbiota in the colon are known to metabolize a great number of drugs, therefore, it is important to understand the stability of these hormones in the presence of colonic flora before developing formulations. The aim of this study was to investigate the stability of three progestogens: progesterone, and its two synthetic analogues, medroxyprogesterone acetate (MPA) and levonorgestrel (LNG), in the presence of human colonic microbiota. Progesterone, MPA, and LNG were incubated in mixed fecal inoculum (simulated human colonic fluid) under anerobic conditions. Progesterone was completely degraded after 2 h, whereas levels of MPA and LNG were still detectable after 24 h. The half-lives of progesterone, MPA, and LNG in fecal inoculum were 28, 644, and 240 min, respectively. This study describes the kinetics of colonic microbial metabolism of these hormones for the first time. MPA and LNG show promise for delivery to the colon, potentially improving pharmacokinetics over current oral delivery methods.

Following oral administration, the bioavailability of progesterone is low and highly variable. As a result, no clinically relevant, natural progesterone oral formulation is available. After oral delivery, first-pass metabolism initially occurs in the intestines; however, very little information on progesterone metabolism in this organ currently exists. The aim of this study is to investigate the contributions of liver and intestine to progesterone clearance. In the presence of NADPH, a rapid clearance of progesterone was observed in human and rat liver samples (t_1/2 2.7 and 2.72 min, respectively). The rate of progesterone depletion in intestine was statistically similar between rat and human (t_1/2 197.6 min in rat and 157.2 min in human). However, in the absence of NADPH, progesterone was depleted at a significantly lower rate in rat intestine compared to human. The roles of aldo keto reductases (AKR), xanthine oxidase (XAO) and aldehyde oxidase (AOX) in progesterone metabolism were also investigated. The rate of progesterone depletion was found to be significantly reduced by AKR1C, 1D1 and 1B1 in human liver and by AKR1B1 in human intestine. The inhibition of AOX also caused a significant reduction in progesterone degradation in human liver, whereas no change was observed in the presence of an XAO inhibitor. Understanding the kinetics of intestinal as well as liver metabolism is important for the future development of progesterone oral formulations. This novel information can inform decisions on the development of targeted formulations and help predict dosage regimens.

Antibody–drug conjugates (ADCs) constitute a rapidly expanding category of biopharmaceuticals that are reshaping the landscape of targeted chemotherapy. The meticulous process of selecting therapeutic targets, aided by specific monoclonal antibodies’ high specificity for binding to designated antigenic epitopes, is pivotal in ADC research and development. Despite ADCs’ intrinsic ability to differentiate between healthy and cancerous cells, developmental challenges persist. In this study, we present a rationalized pipeline encompassing the initial phases of the ADC development, including target identification and validation. Leveraging an in-house, computationally constructed ADC target database, termed ADC Target Vault, we identified a set of novel ovarian cancer targets. We effectively demonstrate the efficacy of Surface Plasmon Resonance (SPR) technology and in vitro models as predictive tools, expediting the selection and validation of targets as ADC candidates for ovarian cancer therapy. Our analysis reveals three novel robust antibody/target pairs with strong binding and favourable antibody internalization rates in both wild-type and cisplatin-resistant ovarian cancer cell lines. This approach enhances ADC development and offers a comprehensive method for assessing target/antibody combinations and pre-payload conjugation biological activity. Additionally, the strategy establishes a robust platform for high-throughput screening of potential ovarian cancer ADC targets, an approach that is equally applicable to other cancer types.

This paper presents a practitioner report of two exemplar European Regional Development Fund (ERDF) projectswithin Cymru (Wales). Namely analysing the AgorIP and Celtic Advanced Life Science Innovation Network (CALIN) businessand research support projects within the context of Regional Innovation Systems (RIS) (Cooke et al, 2004; Pino & Ortega,2018). Cymru has had a long history tied to innovation with Llywodraeth Cymru (Welsh Government) placing the need toencourage Research Development & Innovation (RD&I) and Small and Medium Enterprises (SME) competitiveness at theforefront of their vision for Cymru’s future economy. Both lead by Prifysgol Abertawe (Swansea University), the AgorIP andCALIN projects had different delivery models, AgorIP having secondees in external Cymru HEIs and GIG Cymru UHBs (NHSWales University Health Boards) that supported the delivery at the main hub, and CALIN, a partnership between three Cymruand three Irish HEIs. Jointly supporting over 300 enterprises and organisations across their lifetimes, the projects' outcomesoffer the potential to learn from previous publicly funded business support initiatives within the Cymru RIS. This paper willuse these outcomes to inform future Cymru RIS support projects that could learn from and improve on the operations ofthose before it. These new projects should focus on sharing capabilities and avoiding duplication where possible,incorporating and utilising the individual capabilities and knowledge bases of Cymru's HEIs and Science Parks, with the abilityto work on projects that combine organisations across Cymru and beyond. Further, the projects should adopt AI-enabledsoftware as a ‘shopfront’ to engage with users, automate the creation of RIS networks, and provide business supporttemplates and training that can be supplemented by additional support from project partners.

Marine macroalgae, microalgae, and associated microorganisms are increasingly recognised as valuable sources of bioactive compounds with applications across biotechnology and health. The environmental and ecological conditions they inhabit shape their metabolite diversity, leading to the production of high-value compounds such as sulphated polysaccharides, lipids, pigments, phenolics, and peptides. These compounds exhibit conserved biological activities that underpin potent antioxidant, anti-inflammatory, cytotoxic, and pro-regenerative effects with strong potential for translation. Although external factors drive rich metabolite diversity, continual variation can also lead to translational constraints including heavy-metal accumulation, inconsistency in extract composition, and regulatory complexity. This review examines the environmental drivers of metabolite diversity and the functional potential of bioactives derived from marine algae. We focus on their translational application within four areas of growing interest: nutraceuticals, cosmetics, regenerative medicine, and oncology, where emerging evidence suggests their promise as next-generation bioactive ingredients and therapeutic leads. In addition, insights from Irish and Welsh Small and Medium Enterprises (SMEs) are collated to identify key bottlenecks in commercialisation and the requirements for effective marine biodiscovery pipelines. We consider the importance of controlled cultivation, standardised analytics, preclinical testing platforms, and collaborative innovation ecosystems and highlight the need for coordinated scientific, technical, and regulatory advances to unlock the full translational potential of marine-derived compounds.