World First — Clever Engineering and Flexible Technology Solves a Nanoparticle Challenge

What was the challenge?

It is not every day that you get to solve a unique problem. But that’s exactly what happened when a collaboration with researchers at the University of Melbourne led to a world first breakthrough in scalable Metal Phenolic Network (MPN) nanoparticle production.

About a year ago at the 14th Nanomedicines Conference on Sydney Harbour, I was one of the fortunate people to witness the presentation by Prof Frank Caruso of Chemical Engineering, Melbourne University, describing the effectiveness of Metal Phenolic Networks (MPNs) to target specific organs. This science is extraordinary given it has the potential to create organ specific nanoparticles for drug delivery.

However, translating this science into scalable production posed significant hurdles. The method can be very labour intensive, and particularly difficult to automate as there are multiple order and time sensitive components required.

Engineering meets chemistry

During discussions with postdoctoral researchers Dr Christina Cortez-Jugo and Dr Qingqing Fan, it became clear that existing off the shelf technologies that have been developed for LNPs couldn’t easily handle the unique requirements of newer MPN formulations. Specifically, the requirement to sequentially introduce multiple distinct components with precisely controlled timing and order presented a challenge not addressed by current commercial technologies.

Micropore Technologies have already solved many issues of scaling complex chemistries in the past. ATA Scientific created a test rig with the Pathfinder system and some very cool modifications at our disposal. Theories around flow dynamics and introduction speed were numerous, and at times perplexing. In practice, with the help of Dr Jingqu (Rachel) Chen we simply set up our best estimate to see if we could even make the nanoparticles. Post processing and subsequent analysis on the Malvern Panalytical Zetasizer Ultra Red proved we had extraordinary success!

Scalable reality

An experiment plan followed, to demonstrate the scalability of MPN NPs using Pathfinder. The following was proposed:

1. Batch comparison: Produce both manual and Pathfinder-fabricated MPN NPs using 2–3 well-reported formulations with varying components. These will be scaled at 2 mL, 5 mL, 10 mL, 50 mL, and 100 mL volumes, with comparison of size, zeta potential, encapsulation efficiency, and in vivo performance across batches.
2. Functional testing: Preparation of larger-scale batches of MPN nanoparticles loaded with various therapeutic small molecule drugs using the Pathfinder system to evaluate functional performance. Results will be benchmarked against manually synthesized nanoparticles using identical analytical parameters.

Why does this matter?

Without scalable and reproducible production, the entire MPN project could have remained stuck in the lab. It is now clear that the flexibility of the Micropore Technologies Pathfinder uniquely resolves this challenge — not just at lab scale, but full GMP production is clearly possible given this technology is used to create litres/minute, opening the opportunities for treatments with the MPN technology.

What’s next?

Buoyed by the preliminary results, the team have submitted an abstract to the A-RNA25 conference later this year entitled “Bioactive metal-organic nanoparticles: a versatile platform for RNA delivery”. This is a presentation not to be missed — visit www.a-rnameeting.org.au for more details.

For more information on how the Pathfinder may solve your nanoparticle needs, contact Pete Davis, ATA Scientific +61 0417 778 971 or email pdavis@atascientific.com.au

Image caption: Cargo-loaded MPNs NPs. Image has been cropped from the original (https://doi.org/10.1002/anie.202312925) and is courtesy of the study authors under CC BY 4.0