The Drug Evaluation Hub

• Mapping multi-organ absorption, distribution, metabolism, and excretion (ADME) of drug candidates in individual and interconnected organs and tissues.
• Tailoring PK studies for organ specific physiology and biochemistry.
• Assessing first-pass metabolism in liver models and systemic circulation to evaluate bioavailability.
• Evaluating the impact of ocular barriers in eye models on drug absorption and local bioavailability.
• Investigating cross-talk between organs to understand drug effects and metabolism.
• Performing targeted PK profiling for site-specific drug delivery, including intramuscular and subdermal approaches in limb models.
• Investigate the influence of a fully functional immune system on drug kinetics, with specific focus on immune-modulating drugs.
• Profile kidney-model excretion patterns for renal drug clearance, and hepatic drug clearance in liver models.
• Quantify drug and metabolite concentrations in different tissue compartments to understand distribution within and between organs.

• Assess the immunomodulatory effects of treatments using integrated immune system models.
• Evaluate drug effects on organ haemodynamics and vascular integrity.
• Analyse drug effects on liver function, including bile production and enzyme regulation.
• Test the gastrointestinal influence of drugs on the gall bladder.
• Measure the influence of therapeutic agents on the spleen, focusing on blood filtration and immunological functions.

Kidney: 

• Evaluate drug-induced renal cell injury using biomarkers like KIM-1, NGAL, and cystatin C.
• Monitor for changes in glomerular integrity and tubular function following drug exposure.
• Investigate mechanisms of drug-induced acute kidney injury and chronic kidney disease progression.
• Assess post-toxic renal recovery and regenerative capabilities in isolated and interconnected kidney models.
• Study the effects of repeated and chronic dosing on renal architecture and filtration capacity.

Liver:

• Quantify liver enzyme alterations to detect hepatocellular damage.
• Map the impact of drugs on liver metabolism and bile flow dynamics.
• Utilise the LIVING-LIVER to investigate hepatocyte apoptosis induced by toxic compounds.
• Examine hepatoprotective strategies and their ability to mitigate drug-induced liver injury.
• Analyse the liver’s role in systemic toxicity when integrated with other organ models.

Spleen:

• Investigate splenic filtration and immune cell populations in response to drug exposure.
• Assess the impact of drug exposure on splenic architecture and the potential for splenomegaly or hypersplenic changes.

Eye:

• Assess the effects of drugs on ocular pressure, fluid dynamics, and retinal health.
• Evaluate the potential for drug-induced ocular surface damage.

Limb:

• Evaluate the structural integrity of blood vessels and endothelial function in response to toxicological agents.
• Investigate the mechanisms of drug-induced vasculitis and thrombosis.
• Assess the effects of drugs on muscle health, including potential for myopathy.
• Evaluate the recovery of limb vascular and muscular function after exposure to toxic substances.

Multi-Organ:

• Create multi-LIVING-ORGAN scenarios to assess how drugs metabolised by one organ may become toxic to another, simulating whole-body responses.
• Introduce toxic agents across interconnected organ systems, then evaluate immune system activation and inflammatory responses. 
• Investigate the compensatory mechanisms involved in multi-organ toxicity.

• Simulate clinical polypharmacy scenarios across different organs and evaluate DDIs.
• Investigate altered drug metabolism within the liver and determine enzyme induction or inhibition.
• Evaluate the impact of DDIs on immune function, particularly when combining immunosuppressants with other treatments.
• Investigate renal DDIs, with specific focus on drug metabolite excretion.
• Determine the implications of DDIs on pulmonary function, and assess treatments targeting respiratory conditions.
• Assess the impact of DDIs within an eye model, and measure ocular pressure and fluid dynamics in eye models, which are critical for glaucoma medication developments.
• Evaluate the interactions between blood components and drug administration in a circulating immune compartment.
• Examine the effects of DDIs on limb perfusion and vascular function, with emphasis on vasoactive drugs.

• Conduct nerve safety assessments with integrated limb and immune system models, which can identify reflexes and efferent/afferent responses.
• Utilise kidney models to examine to renal safety and detect changes in glomerular filtration rate and tubular reabsorption.
• Evaluate ocular safety, ensuring no impairment to eye structures.
• Study the immunological drug safety in models with immune system integration, monitoring for example, hypersensitivity, cytokine response syndrome or immunosuppression.
• Investigate liver function and drug safety, particularly focussed on hepatotoxicity and bile flow disturbances.
• Understand the potential impact of drugs on splenic structural integrity and function; an organ often overlooked in pharmacological safety.