The field of drug delivery is experiencing unprecedented innovation, with nanoparticle-based systems leading the charge in developing more precise and effective therapeutic approaches. From lipid nanoparticles that delivered COVID-19 vaccines to advanced formulations targeting specific diseases, researchers are pushing the boundaries of how we deliver medicine to the human body.
Dr. Freya Leech is a researcher at NanoFCM, a company that provides platforms for single-particle level analysis of nanoparticles. With expertise spanning formulation science and characterization technologies, she has been at the forefront of developing analytical methods that help researchers better understand and optimize nanoparticle-based drug delivery systems.
Technology Networks invited Leech to discuss the current challenges and future prospects in nanoparticle drug delivery.
Steven Gibney (SG):
Science Writer
Technology Networks
Steven has a BSc in Pharmacology and a Masters in Bioscience from the University of Leeds, as well as a Ph.D. in Pharmacy from the University of Nottingham. After finishing his Ph.D. he spent two years working at an agency as a medical writer. Wanting to further develop his communication skills he joined Technology Networks as a science writer in 2023. In his current role, he is responsible for creating custom written content and also contributes to the development of digital content.
Can you give us an overview of your current research and work area, and how does it relate to drug delivery?
Dr. Freya Leech is a researcher at NanoFCM, a company that produces nano flow cytometers for advanced characterization of nanoparticles. Her work focuses on single particle analysis techniques that help researchers better understand and optimize nanoparticle-based drug delivery systems.
I am a researcher at NanoFCM. We are a company that produces a nano flow cytometer, which is an instrument that allows for single-particle level analysis of nanoparticles in the range of 40 to 1000 nanometers. About half of what we do is nanomedicines and nanoformulations. We also offer advanced quantification for nucleic acid payloads, we can measure copy number per particle and encapsulation efficiency, as well as surface density.
SG:
Science Writer
Technology Networks
Steven has a BSc in Pharmacology and a Masters in Bioscience from the University of Leeds, as well as a Ph.D. in Pharmacy from the University of Nottingham. After finishing his Ph.D. he spent two years working at an agency as a medical writer. Wanting to further develop his communication skills he joined Technology Networks as a science writer in 2023. In his current role, he is responsible for creating custom written content and also contributes to the development of digital content.
What do you think is one of the biggest challenges when translating therapeutics from development into effective treatments?
FL:
Dr. Freya Leech is a researcher at NanoFCM, a company that produces nano flow cytometers for advanced characterization of nanoparticles. Her work focuses on single particle analysis techniques that help researchers better understand and optimize nanoparticle-based drug delivery systems.
Going from bench to bedside, there's quite a few jumps that need to be made. When you're in the formulation stage, the idea is to run as many screening tests as possible to figure out what materials and ingredients you can use to generate stable nanoparticles suitable for the desired purpose. Half of the battle is getting a nanoparticle in the size that you want with an appropriate distribution of your payload using the materials that you have.
Once you've got a library of nanoparticles, you make the leap to functional assays that include in vitro screens and functional cell work. Then you go from the in vitro work into in vivo mouse studies, then hopefully to clinical studies. But the amount of jumps required means that not every stage is going to be indicative of what happens at the next stage.
The best strategy is to start with as many lipids or polymers, or whatever you're making your nanoparticles from, as possible. This way, when you lose options going to the next stage, you've still got viable options. Probably the biggest challenge is designing nanoparticles to minimize loss going from each stage to the next.
Science Writer
Technology Networks
Steven has a BSc in Pharmacology and a Masters in Bioscience from the University of Leeds, as well as a Ph.D. in Pharmacy from the University of Nottingham. After finishing his Ph.D. he spent two years working at an agency as a medical writer. Wanting to further develop his communication skills he joined Technology Networks as a science writer in 2023. In his current role, he is responsible for creating custom written content and also contributes to the development of digital content.
What are some of the limitations with current nanoparticles, whether it's drug loading capacity or kinetics, and how can we address these?
FL:
Dr. Freya Leech is a researcher at NanoFCM, a company that produces nano flow cytometers for advanced characterization of nanoparticles. Her work focuses on single particle analysis techniques that help researchers better understand and optimize nanoparticle-based drug delivery systems.
At the moment, because the technology of how you make nanoparticles is still somewhat in its infancy, you get a lot of heterogeneity with nanoparticles. For regulatory aspects, you want things that are all the same size or as close to the same size as possible, with an even distribution of any targeting molecules and payload, whether that's a drug or nucleic acid therapeutics. From a formulation perspective, it's getting things as consistent as possible, because consistency is what makes a reliable dose when you administer it. In terms of kinetics, it's finding materials that produce stable nanoparticles that don't need extreme storage conditions, that are biocompatible and that are non-toxic. Although for some formulations, like vaccines, you want it to be non-toxic but you still want immunogenicity. So, it's finding materials that balance your needs.
SG:
Science Writer
Technology Networks
Steven has a BSc in Pharmacology and a Masters in Bioscience from the University of Leeds, as well as a Ph.D. in Pharmacy from the University of Nottingham. After finishing his Ph.D. he spent two years working at an agency as a medical writer. Wanting to further develop his communication skills he joined Technology Networks as a science writer in 2023. In his current role, he is responsible for creating custom written content and also contributes to the development of digital content.
What are some of the biggest hurdles in terms of regulating nanoparticles?
FL:
Dr. Freya Leech is a researcher at NanoFCM, a company that produces nano flow cytometers for advanced characterization of nanoparticles. Her work focuses on single particle analysis techniques that help researchers better understand and optimize nanoparticle-based drug delivery systems.
Heterogeneity is a major issue. The biggest thing with regulatory approval is getting methods to test and reliably assess the particles. A lot of the regulation at the moment for nanoparticles relies on bulk measurements like dynamic light scattering, which is great for a population perspective but tends to favor a certain window and extrapolate down to smaller particles. Techniques that use single particle analysis, where you're looking at every particle on an individual level, tell you more about where your payload is and whether it's correlated to any targeting molecules. The challenge is getting accurate methods to determine what's in your formulation.
From a regulation perspective, the terminology is still trying to catch up because the possibilities when formulating are astronomically high. The number of lipids you can use in lipid libraries for lipid nanoparticles (LNPs) are insanely large. Getting the legal framework to catch up with these different terms is difficult – we use LNPs as a catch-all, but there are many sub-particle types. The terms and definitions aren't standardized or particularly regulated, and the methods of measurement and production aren't controlled. Getting all the regulatory pathways and terminology caught up to where the research will be quite difficult.
Science Writer
Technology Networks
Steven has a BSc in Pharmacology and a Masters in Bioscience from the University of Leeds, as well as a Ph.D. in Pharmacy from the University of Nottingham. After finishing his Ph.D. he spent two years working at an agency as a medical writer. Wanting to further develop his communication skills he joined Technology Networks as a science writer in 2023. In his current role, he is responsible for creating custom written content and also contributes to the development of digital content.
What developments are you seeing in relation to artificial intelligence (AI) in drug delivery optimization and characterization?
FL:
Dr. Freya Leech is a researcher at NanoFCM, a company that produces nano flow cytometers for advanced characterization of nanoparticles. Her work focuses on single particle analysis techniques that help researchers better understand and optimize nanoparticle-based drug delivery systems.
I can see AI being very helpful for rational design and smart screening. When I was doing my PhD with one foot in formulation and one foot in immunology, people didn’t talk to each other across different disciplines. You formulate a particle and then it becomes a cell development problem. Then you get a library of materials to test using in vitro assays, and then it becomes a mouse study problem. Getting the crosstalk between different steps – between the therapeutic and formulation – I can see AI being helpful for that integration.
SG:
Science Writer
Technology Networks
Steven has a BSc in Pharmacology and a Masters in Bioscience from the University of Leeds, as well as a Ph.D. in Pharmacy from the University of Nottingham. After finishing his Ph.D. he spent two years working at an agency as a medical writer. Wanting to further develop his communication skills he joined Technology Networks as a science writer in 2023. In his current role, he is responsible for creating custom written content and also contributes to the development of digital content.
What therapeutic areas do you think will be transformed by nanoparticle drug delivery over the next decade?
FL:
Dr. Freya Leech is a researcher at NanoFCM, a company that produces nano flow cytometers for advanced characterization of nanoparticles. Her work focuses on single particle analysis techniques that help researchers better understand and optimize nanoparticle-based drug delivery systems.
The obvious one is gene delivery because the possibilities are incredible, whether you're looking at siRNA for gene silencing or CRISPR–Cas9 delivery. We've seen a huge increase in CRISPR–Cas9 delivery because you can deliver the protein and nucleic acid in one formulation. Also, we've already seen a massive uptick in mRNA vaccines, but I think gene delivery is going to be the biggest area.
Nanoparticles can do many wonderful things – they can improve tolerability of highly toxic drugs. We've seen use with drugs like doxorubicin, which is affectionately called the “red devil.” This improves both uptake and availability, because you can get away with a lower dose if you're getting higher uptake by putting it in a nanoparticle. For drugs that metabolize very quickly and need high doses, if you can stealth ship them in a nanoparticle, that's going to improve outcomes.
Even as production methods get better – with methods like microfluidics, you can get really reliable production – this could be used in personalized medicine as well. But I'm going to stick with gene delivery because that's the really exciting stuff.
