Good news for people who hate needles: future vaccines could be delivered by a gentle puff of air to the arm. Scientists say the medicine being pushed through the skin, with just a little pressure, feels like being "hit with a Nerf bullet” - much less painful than a jab.
Using powdered vaccines that don’t require refrigeration and a system driven by compressed gas, they believe their “MOF-Jet” could easily deliver therapeutics against cancer and other diseases in a relatively painless way. The idea for the project was formed out of pandemic-induced boredom, according to principal investigator Professor Jeremiah Gassensmith.
Prof Gassensmith, of the University of Texas, had ordered cheap pieces of a compressed gas-powered jet injection system to mess around with while stuck at home. Later, after everyone was back on campus, he handed the pieces over to Yalini Wijesundara, a graduate student in the lab, with the instructions, “See what you can do with this.”
She had previously researched other jet injectors dating back to the 1960s that use compressed gas to inject a narrow stream of fluid. The PhD student worked out that if the injectors could be modified to fire solids they could deliver cargo encased in metal-organic frameworks, or MOFs, as well.
The frameworks are porous, crystalline structures that act like molecular “cages” to encapsulate a wide variety of materials, including nucleic acids and proteins. By combining the jet injector with the lab’s existing work on MOFs, Ms Wijesundara created a “MOF-Jet.”
The jet can deliver powders to cells by, quite literally, shooting them in with air. Jet injectors previously saw widespread use in the military, but they were painful and the fluid often splashed back, potentially spreading other diseases such as Hepatitis B.
A modern-day descendant is the “gene gun” - used in veterinary medicine and can cost tens of thousands of pounds. Those devices also shoot biological cargo into cells. In the study, the cargo is attached to the surface of a metal microparticle, typically made of gold or tungsten.
But once it penetrates the skin, the metal particles remain there and can speed up the degradation of the biological material. A different strategy would be to put the cargo inside a MOF.
Prof Gassensmith’s group previously worked with the MOF called zeolitic-imidazolate framework eight, or ZIF-8. Ms Wijesundara said: “Compared to gold, it’s cheap and protects biological materials, such as nucleic acids. We can also store vaccine formulations within it as powders at room temperature, which eliminates the need for the extremely cold temperatures many liquid vaccines require.”
The team encased a variety of biological materials within ZIF-8, which protected them from being broken down too quickly. To deliver the materials into cells, the team used their own modified, gene gun-inspired “MOF-Jet.”
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Ms Wijesundara created “bullets” for the device, each loaded with a dose of functionalized ZIF-8, and a puff of gas fired the powdered formulation into cells, which she said was as easy as “pointing and shooting.” They tested their system and showed that the MOF-Jet delivered a ZIF-8-encased gene to onion cells and a ZIF-8-encased protein to mice.
Prof Gassensmith said the "blast" from the injector feels “like you got hit with a Nerf bullet.” By tinkering with the MOF-Jet, Ms Wijesundara realised that cargo release could be tuned by simply changing the injector’s carrier gas.
She said: "If you shoot it with carbon dioxide, it will release its cargo faster within cells; if you use regular air, it will take four or five days." The researchers say that means that the same drug could be released over different timescales without changing its formulation.
Prof Gassensmith added: "Once we realised that, it opened up a lot of possibilities.” The team is now using that method to deliver chemotherapeutics as a potential treatment for melanoma, the most serious form of skin cancer.
They say that because the MOF-Jet can disperse material over a wide area, it could distribute a cancer therapeutic into a melanoma more evenly than with a needle, which is the current delivery method. The findings are due to be presented at a meeting of the American Chemical Society.
