The pharmacogenomics and delivery of therapeutics (PDT) group performs research and development with particular focus directed at the interface of therapeutic molecule delivery, the development of therapeutic strategies and the study of the pharmacokinetic aspects of therapy delivery. The PDT unit integrates expertise in chemistry, biology, polymer science and pathophysiology. Within the PDT group, the scientific principles of medicine formulation are applied to develop delivery systems for conventional but challenging therapeutic molecules and also for products of biotechnology, unveiling new treatment strategies to improve or generate therapeutic benefits. A natural synergy with the area of pharmacogenomics is clear, as this field aims at increasing the understanding of inter-individual variability in drug efficacy and safety. Given that the studied genes and pathways also play a role in controlling levels of other exogenous and endogenous compounds, pharmacogenomics studies in the context of chemically induced or hormonal dependent pathologies are performed within the PDT unit aimed at unveiling genetic factors that can contribute to disease risk.
Mucosal drug delivery approaches
Emerging new therapeutic molecules (e.g. proteins, peptides, antigens, growth factors, cytokines) display biophysical properties that are different from current small molecular weight drugs: they cannot cross biological barriers and/or undergo degradation in biological environments. Consequently, delivery systems capable of effectively protecting molecules, while providing site-specific delivery, are demanded. This approach within the TDP unit enables the use of mucosal delivery as alternative to parenteral administration. In parallel, certain specific diseases will benefit from the controlled release of conventional drugs, requiring concomitant strategies for site-specific delivery, such as in the cases of cystic fibrosis and tuberculosis. In summary, this TDP research objective explores different approaches for the mucosal delivery of novel biopharmaceutical drugs including conventional drugs, specifically focusing on lung delivery that controls the location of release, while also protecting these delivery vehicles.
Pharmacogenetic determinants of therapeutic outcome
The effects of foreign chemicals in vertebrates depends upon their metabolism and transport by proteins that are highly variable in activity among individuals, leading to variable outcomes. Polymorphic variants in genes coding for drug metabolizing enzymes and transporters (DMET) are analysed within the TDP unit to evaluate the degree of inter-individual and inter-ethnic variability and to understand their role in the differential response to therapeutic drugs. Examples of ongoing studies focuses on anti-malarial, anti-inflammatory and cardiovascular drugs.
Retinal gene therapy and therapeutic approaches
The eye is an attractive target for gene therapy because it is an accessible and immune-privileged organ and, due to its small size, only a small amount of therapeutic agent is necessary to obtain a significant therapeutic effect. The relevance of the retina for gene therapy derives from its prominent role in ocular disorders. The chronic, progressive nature of many retinal diseases will require long-term, stable expression of transgenes over years or even decades. Our work within the TDP aims to develop expression systems for genes with potential therapeutic effect against these diseases. The major difficulty in treating diabetic retinopathy and retinal neovascular pathologies lies in the fact that the exact mechanisms underlying these diseases are still unclear. To develop new therapeutic strategies for ocular pathologies using gene therapy approaches the TDP unit is elucidating the mechanisms that contribute to these diseases and identifying new therapeutic agents, based on growth factors and siRNA strategies.
Genetic and regulatory factors as modifiers of disease risk
Inter-individual variability in risk for disease depends multiple factors. This includes gene structure variants, gene regulation by endogenous and exogenous factors and gene transcription. The activities of drug metabolizing enzymes and transporters (DMETs) are subject to complex transcriptional regulation by various stimuli. The TDP unit is focused on understanding the factors that control DMET gene expression under situations of chemical challenge (such as during chemotherapy regimens). Ongoing studies within the TDP unit examines the crosstalk between DMET gene regulation and oxygen status, lipid homeostasis and inflammation. These are critical factors in pathologies such as cancer, diabetes, and cardiovascular disease.