PhD in Pharmacy

Though immunotherapy has revolutionized the treatment of cancer to improve disease outcomes, an array of challenges remain that limit wider clinical success, including low rate of response and immune-related adverse events. Targeting immunomodulatory drugs to therapeutically relevant tissues offers a way to overcome these challenges by potentially enabling enhanced therapeutic efficacy and decreased incidence of side effects. Research highlighting the importance of lymphatic tissues in the response to immunotherapy has increased interest in the application of engineered drug delivery systems to enable specific targeting of immunomodulators to lymphatic tissues and cells that they house. Microneedle arrays are minimally-invasive devices that painlessly, and without drawing blood, penetrate the skin’s stratum corneum barrier. This allows delivery of a range of substances that would otherwise not be able to move into or across the skin. We have recently found that, while low molecular weight drugs are rapidly absorbed into blood via the dermal microcirculation when delivered using our microneedles, macromolecules and nanoparticles are first transported to the lymphatic system, either by interstitial fluid drainage or cellular migration following specific uptake by potent immune antigen-presenting cells in the epidermis and dermis. This phenomenon creates a unique opportunity for specific targeting of therapeutic agents to the lymphatic system. In this project, we will load our dissolving microneedle platforms with drug-containing nanoparticles engineered to prevent absorption by the dermal microcirculation and enhance retention in the lymphatic system. By using targeted nanoparticle approaches, we plan to avoid toxicity associated with systemic delivery of chemotherapies, whilst exploiting active drug targeting through surface carbohydrates and/or antibodies.