Drugs given to the whole body can be too much of a shotgun approach, damaging cells that aren’t meant to be targeted. A new study has found that cloaking drugs inside red blood cells could help guide powerful but toxic antibiotics to target bacteria.
Bacteria are increasingly developing resistance to our best antibiotics, leaving doctors with fewer and fewer treatment options. In many cases, we’re down to our last-resort drugs, such as those that induce severe side effects within the body.
But there may be ways to target these drugs more precisely. A few years ago scientists at McMasters University in Canada developed what they called “super-human red blood cells” – essentially, they pull out the innards of normal blood cells and stuff them full of drugs instead. When the hybrid blood cells are injected back into the body, they theoretically should be able to carry the drug payload safely, without the immune system attacking them.
In the new study, the team tackled a remaining problem – how do you get the hybrid blood cells to home in on the desired target? They coated the outside of the blood cells in an antibody that targeted the bacteria species they were trying to kill, which makes them accumulate around the bugs and deliver their drug payload more precisely.
The researchers tested the drug delivery system with an antibiotic called Polymyxin B (PmB), which is effective at killing bacteria that are resistant to other drugs. But that comes at a cost to healthy cells, with the potential for kidney damage, neurological problems, and other serious side effects. As such, it’s considered a last-resort antibiotic.
In cell culture tests in vitro, the team loaded the blood cells with PmB and targeted them to drug-resistant E. coli. They found that the cells had a loading efficiency of around 90%, and were effective in delivering PmB to the bacteria in levels high enough to kill them. To test the targeting, the team also exposed a different bacterium, Klebsiella aerogenes, to the hybrid cells coated with E. coli antibodies, and found that they were insufficient to kill the bugs. That, the team says, shows that the selective targeting works.
The researchers say that this approach has a number of advantages. Not only does it keep the drug payload from affecting healthy cells, but because red blood cells have a long lifespan of around 120 days, they have plenty of time to reach the targeted sites. The technique could also reduce the number of doses required and the amount of drug per dose.
“Essentially, we are using red blood cells to conceal this antibiotic within so it can no longer interact or harm healthy cells as it passes through the body,” said Hannah Krivic, lead author of the study. “We designed these red blood cells so they could only target bacteria we want them to target.”
The team says that future work will investigate the technique’s potential for delivering drugs across the blood-brain barrier to the brain to help treat neurological diseases such as Alzheimer’s.
The research was published in the journal ACS Infectious Diseases.
Source: McMaster University