Scaling-Up plant based Nanocarriers for BIOpharmaceuticals (SUNBIO)

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THE CHALLENGE: Biopharmaceuticals are growing at a rate double of traditional pharma owing to the unique properties of microorganisms including their biocompatibility and technology that cannot be easily replicated in the lab. The UK needs to rapidly expand its biopharmaceutical manufacturing capacity in order to access a greater fraction of the global market and realise the economic benefits of job creation and exports."Bugs as drugs" have been seen historically to treat diseases including cancer which is inspiring the next generation of treatment options for cancer patients, particularly those with chemotherapy-resistant, recurrent, or metastatic disease. However, a major challenge for use of "bugs" including bacteria and cancer-killing viruses is they are readily recognised by the immune system and rapidly removed before they can take effect. Our team wants to overcome this challenge through our research so that we can unlock the benefits for more patients, allowing all cancer to be treated with these therapies. The full potential of these medicines can only be realised by enabling their targeted delivery to tumours within the bloodstream whilst simultaneously bypassing the body's defence systems. To do this, we have successfully developed a number of nanocarriers for cancer-killing viruses. Due to their nature, these viruses are sensitive to degradation and elimination, however our bubble-like particles not only shield them for targeted delivery, but the packaging is done in a way that maintains the viruses viability and functionality - the first time this has been shown. Synthetic alternatives (e.g. polymers) are incompatible with biological therapies due to exposure to harsh conditions (heat, solvents, pressure) during production as well as being known as highly inefficient.OBJECTIVES: Here, we focus on materials derived from natural sources (e.g. plants) that are non-toxic, biocompatible, sustainable and biodegradable. Utilising the 'safe and sustainable by design' (SSbD) framework, a voluntary approach to guide the innovation process for chemicals and advanced materials as recommended by the European Commission, we will scale-up the manufacture of our bioinspired nanocarriers to be 'clinic ready'. The scope of experiments required to optimise these systems requires high throughput microfluidics which we have developed 'in house'. Our microfluidics device can rapidly mix and produce high quality nanoparticle encapsulated viruses at large scale with the promise to outperform current commercial devices. We now want to optimise our device and consider improved mixing speed, reproducibility, productivity/scalability as well as reduced cost.BENEFIT: So far, biological therapies have not lived up to their potential due to their poor delivery in the body. Here we present a sustainable solution to scale up new modalities for the treatment of all cancers by formulating them within bioinspired nanoparticles, specifically designed to maintain the functionality of these sensitive biological agents and provide targeting capabilities. This innovative project fully aligns with the EPSRC core theme for the development of a pipeline for controllable, reproducible, and scalable production of our bioinspired NP platforms to facilitate clinical translation and unlock the power of biological therapies. This will have applications across the growing biopharma market where low therapeutic index, immunogenicity and lack of scale-up are major barriers to entry for these therapies. Whilst we use viruses as an exemplar, our platforms can be used to package any drug/agent (e.g mRNA) for wider clinical application.