Multiple time-delayed drugs could be given in single injection, say scientists

Multiple injections for vaccinations could become a thing of the past, according to scientists who have developed an approach for delivering many doses of different substances in just one jab.

The technology involves encapsulating drugs or vaccines within tiny particles made of biodegradable polymers. Depending on their makeup, these polymers break down at different points in time, releasing their contents into the body.

Researchers say the approach could allow multiple vaccines to be delivered at once and remove the need for booster jabs. It may also prove handy in treatments for allergies, diabetes and even cancer where multiple injections are needed.

Researchers say it could prove valuable in developing countries, potentially allowing all childhood vaccines and their boosters to be given in one shot.

“One of the main limitations there is access to vaccines and the fact that you have to come back several times in order to get immunity from the pathogen,” said Ana Jaklenec, co-author of the research from the Massachusetts Institute of Technology. “A child or a baby is usually seen once, sometime around the birth time by some sort of healthcare worker.”

Writing in the journal Science, Jaklenec and colleagues describe how they developed the novel technique using biodegradable polymers already approved for use in humans.

The process, they reveal, involves making tiny silicone moulds – rather like ice cube trays – into which the biodegradable polymers are pressed and removed to form an array of box-like structures, each about 400 micrometres across. These are then filled with the required drug or vaccine and allowed to dry.

A lid, made from the same polymer, is then lined up on top of each micro-box and the system is briefly heated to seal it and prevent the drug or vaccine from leaking out.

When injected into the body, the boxes remain sealed until the polymer disintegrates – an event which occurs rapidly, with the timing dependant on the makeup of the polymer itself.

“What’s novel here is that the sharpness of how quickly the drug releases from the particle and the fact there is no leakage at all from the particle until [then],” said Jaklenec.

To test the approach, the team injected mice with microparticles made from one of three different polymers, each filled with a fluorescent substance. Using imaging techniques, the fluorescent substance was seen to be released at about nine days, 20 days or 41 days, depending on the polymer used.

The team also produced microparticles filled with a polio vaccine and exposed them to an antibody test to see if the vaccine’s potency was affected by the heat sealing: no such problem was detected.

Finally, mice were injected with two sets of microparticles made from different polymers – one designed to break down after about one week and the other after about five weeks – with both containing a protein found in egg white. The animals’ immune response was tracked for 16 weeks.

The results reveal that the filled microparticles triggered a response greater than two regular injections of the same dose of protein spaced four weeks apart. Indeed, the response was on a par with that from two regular injections each with twice the dose – probably down to the microparticles themselves boosting the immune response.

The team say the approach could have myriad applications in medicine and beyond. “ You could use pH sensitive materials [or] you can fill with any type of drug, or therapeutic or sensing drug, so we think it has a lot more application than just vaccines,” said Jaklenec.

But, she added, challenges remain, not least that vaccines are normally stored in refrigerators: “[We] have to stabilise all of these vaccines in the body for a long period of time at elevated temperature,” she said.

Andrew Pollard, professor of paediatric infection and immunity at the University of Oxford, was optimistic, although he noted it was early days.

“Technologies which allow slow or timed release of a dose and thus reduce the ‘needle burden’ of an immunisation programme without compromising protection would be welcomed by healthcare workers, parents and their offspring,” he said.

David Goldblatt, professor of vaccinology and immunology at University College London, said the approach was sophisticated.

But, he warned, hurdles remain, noting that it removed the chance to modify vaccines between doses and that there was no way to adjust the timing of vaccine release after injection. “We prefer to avoid immunising when you might have an active viral infection,” he said. “[What happens] if a child has malaria on the day that the [vaccine dose] is released automatically?”

Nevertheless, he said, the approach could prove revolutionary in helping children in developing countries to receive adequate vaccination. “It could be a game changer for that,” he said.