Mass-Production of Nanoparticles in Medicine: Why Aren’t We There Yet?

Nanoparticles - minuscule delivery vectors capable of travelling where no drug has gone before and providing the right treatment dose at the right time with little to no side-effects, have long been touted as the future of medicine. Dr Vladimir Gubala, lecturer in Chemistry and Drug Delivery at the Medway School of Pharmacy, discusses the challenges and describes the advantages of Vitl's Co-Mix.

Search in any chemistry journal from the past decade and you will find paper after paper identifying new and novel uses for these tiny marvels of bio-engineering. This begs the question – with so much research, why isn’t that future here yet? According to Dr Vladimir Gubala, lecturer in Chemistry and Drug Delivery at the Medway School of Pharmacy, “15 years ago scientists promised nanotechnology would revolutionize the way treatment of cancer happens or it will revolutionize how we go to the doctor with a simple cough and ask him if it’s a virus or a bacterium. However, something must have gone wrong because if you look at the available nanomedicine products there are not that many.” Vitl Life Science Solutions met with Dr Gubala and his PhD students in an effort to understand the challenges, and to see how their Co-Mix programmable laboratory mixer is helping.

Point-of-Care Medical Devices

Dr Gubala has a team of four postgraduate students preparing nanoparticles in the laboratory specifically for human health applications. The particles are similar to those you would find in a point-of-care medical device such as a pregnancy test and either amplify a signal produced by some other reaction, or generate a signal themselves. The whole detection and diagnosis method relies on being able to generate a high signal output when something is there (e.g. indicator of a disease) and very low signal when there is nothing. This is where nanoparticles really have the opportunity to shine over existing methods.

The nanomaterials can be produced in all different shapes and sizes (although their work is usually done with spherical particles as these are the easiest to synthesize), and can then be tagged with a variety of fluorescent materials such as dyes or even proteins. Once created, the particles are thoroughly characterized, which at the moment is an entirely manual process with extensive use of a range of reagents and a lot of manual handling. Without a reliable way to make and test particles on a small scale there is very little hope of reaching mass production. This shows the inherent problem with nanoparticle synthesis, and also sheds some light on why industrial production on a large scale has so far eluded us – a lack of automation.

Currently, the team is only producing very small volumes of nanomaterial and ensuring that even these small volumes are homogeneous is hampered by natural inefficiencies in the way humans can work. This is something which, although small, can make a very big difference in the nano world. Attempts to reduce these inefficiencies are what led Dr Gubala to use the Vitl Co-Mix in his laboratory.

Repeatability and Reliability

Two words that form the cornerstone of all science and two words that immediately create trouble where humans are involved. As Dr Gubala explains, “Anything that gives you the option to automatically start, stop or stop and restart again gives you some control over how reproducible your products are. There’s a big inaccuracy between what we actually produce because the nanomaterial is synthesized under different conditions so what we’re trying to do in our lab is to automate the process as much as we can.Without automation, one day samples are removed [from the shaker] at exactly the right moment, but the next day they could come off five minutes later, and the day after that it ends up being half an hour late.”

As a result, when those particles are characterized, those precious few minutes have meant that there is now a quite heterogeneous mixture or as Dr Gubala succinctly puts it, “If you forget about it you likely create something different.”

Another reason the Co-Mix has received so much adoration from this team is the robustness of the product - they were once buying four mixers per year! Dr Gubala was happy to inform us that his Co-Mix survived the ultimate test of being left in the hands of a large number of his undergraduates. As a lecturer he said there was no higher praise he could offer beyond the confirmation that he considers the Co-Mix “Undergraduate-Proof”.

Testing Nanomaterials

The research then goes from the manufacturing phase into laboratory testing where the team need to accurately mix, shake and incubate, to understand what the material does at different temperatures and under different conditions. This is another part of the process that Dr Gubala feels is hampered by a lack of automation.The Vitl Ther-Mix (soon to be released) enables exactly this – with the same repeatable, controlled sample mixing as the Co-Mix but performed within specific heated modules that offer intimate-contact heating, both from below and with a heated lid, to avoid condensate and help reduce light exposure. Medway School of Pharmacy is already first on the list to start using the Ther-Mix in their lab.