I don’t know about you, but I’ve always preferred making my own antibodies.
Why outsource it? It’s so handy letting my own body do the work of fighting infections while I’m writing articles or teaching, buying groceries for my family, or playing video games. But then again, I’m lucky, because unlike 14 million Americans age 64 and younger who are immunocompromised and 58 million Americans age 65 and older with under-effective immune systems, I’m “immune privileged.”
That means that I don’t have to worry about going once a month to a hospital or clinic for hours of getting intravenous antibody treatments for cancer and a range of other diseases – which would include sitting or lying down with an intravenous bag and a needle stuck in my arm – just so I can, you know, not suffer and die.
But now MIT engineer Patrick Doyle, senior author of the Advanced Materials paper “High-Concentration Antibody Formulation via Solvent-Based Dehydration,” is offering a significant breakthrough. Thanks to him and his colleagues Lucas Atia and Janet Teng, there’s a much faster, simpler treatment without an IV bag and an hour of getting needled, and a far more accessible treatment for people for whom simply getting to the hospital might be a major hassle or even an impossibility. Just a single 2-ml shot of a solution containing solid nanoparticles packed with highly concentrated antibodies.
Why not just stick with the traditional method of suspending therapeutic antibody drugs such as rituximab in water? “You can’t concentrate existing formulations to these concentrations,” says Doyle, who is also the Robert T. Haslam Professor of Chemical Engineering.
He’s not kidding. Typically, antibody solutions need to be at low concentrations such as 10 to 30 mg per milliliter of solution, requiring patients to get 100 ml for a single dose. For comparison, a standard cup of coffee is 250 ml, so fill that cup a little less than half full, and imagine getting a single syringe of that injected into you. So, why not just increase the concentration? As Doyle says, that would “be very viscous and will exceed the force threshold of what you can inject into a patient.”
That’s why in 2023 he and his team harnessed hydrogel particles, so they could pack far more antibodies into single shots. But that method needs a centrifuge, which makes mass-manufacturing more difficult.
“Our first approach was a bit brute force,” says Doyle. “When we were developing this new approach, we said to it’s got to be simple if it’s going to be better and scalable.”
So, his team’s new breakthrough was to make an emulsion by suspending antibody droplets inside pentanol, an organic solvent. After dehydration, the emulsion contains particles of around 360 mg of highly concentrated antibodies per milliliter of solution, plus a minute amount of the stabilizing polymer polyethylene glycol (PEG).
The final step is replacing the pentanol with a mixture of water, salts, and a stabilizing polymer. Because the process needs only a microfluidic setup without any use of a centrifuge, mass manufacturing becomes simpler and more cost-effective, and produces formulations that, once refrigerated, remain stable for four months.
And by changing the flow rate of the solutions containing the droplets, the team can adjust particle size – from 200 microns down to 60. Smaller particles means far less force required for injection. Tests with solutions of particles at 100 microns showed that mechanical force dropped to 20 newtons. As co-author Zheng says, “That is less than half of the maximum acceptable force that people usually try to aim for, so it’s very injectable.”
That means injections with a standard 2-ml syringe could deliver 700 mg of antibodies in a single shot. For patients for whom hospital visits already mean losing paid-work hours of travel time and an hour for an infusion, this streamlined method offers a massive improvement in time, convenience, and comfort.
And for patients facing extreme limitations to mobility, or who live vast distances from hospitals and clinics, mobile medical practitioners could offer MIT microparticle emulsion as a no-fuss, no-muss solution – a literal solution of antibodies in a single injection.
Source: MIT
