Associate Principal Scientist AstraZeneca Cambridge, United Kingdom
Nanomedicines have been steadily growing in importance within the pharmaceutical industry and recently, partly due to the advent of COVID-19, they are at the forefront of R&D pipelines. Nanoparticles (NPs) are particularly attractive as Drug Delivery Systems (DDS) for their ability to improve active pharmaceutical ingredient (API) half-life improving therapeutic index (TI) and opening access to intracellular targets. Whilst many NPs have entered the clinical space, only few made it to market. This talk will offer a perspective of NPs that are currently used in pre-clinical and clinical space as passive DDS, such as polymer nanoparticles, dendrimers, polymeric micelles, lipid nanoparticles, and focus on similarities and differences that make some delivery systems more appropriate for specific cargos over others. Within this section, some case studies of AstraZeneca nanomedicines that have been evaluated in clinical trials will be covered, such as the pegylated dendrimer AZD0466. The second part of the talk will focus on the paradigm shift towards receptor or active targeted DDS. Several efforts have been made to develop novel active targeted systems, comprising of a NP carrying an API as cargo but, functionalised on the surface with ligands able to specifically recognise a membrane receptor of interest, thus increasing selectivity and improving further the TI; none has succeeded clinical trials to date. Active targeting has long promised to reach the selected cell population especially in the oncology field targeting solid and haematological tumours. However, some aspects of receptor enabled delivery have still not been fully investigated such as the importance of reaching the right tissue, the requirements for intracellular release of API, the importance of balancing avidity and affinity of selected ligands and challenges in tumour heterogeneity. The talk will review current advances in the field and highlight challenges in translation between in vitro, in vivo and clinical models. The end goal of this perspective talk is to the shed a light on which are still the gaps in the field of passive and active targeted nanomedicines and reflect on what could be done to fill them in the early development space.<
Learning Objectives:
Upon completion, participant will be able to describe differences between passive and active targeting for nanoparticle delivery systems, including why the field is moving towards receptor targeting
Upon completion, participant will be able to list key questions to address during the development of nanomedicines and also some of the key preclinical studies required to close the gaps
Upon completion, participant will be able to understand mode of action of different nanoparticle delivery systems and why some are better suited for certain class of compounds than others