The technique has the support of pharma companies including GSK and Pfizer, which see it as a way to revive compounds abandoned in development, said Eleanor Stride, who runs the project out of Oxford’s Institute of Biomedical Engineering.
The professor told in-Pharmatechnologist.com the method can be used to help small and large molecule medicines hone in on their targets.
“With all therapies that are currently used – particularly cancer – the major problem is very little of the drug makes it to the target site. That’s true of both conventional and antibody therapy.
“We inject drugs into the bloodstream and they go absolutely everywhere, not straight to the tumour.”
This latest method “encases the drug in a bubble – like a soap bubble.”
The bubble consists of a shell of phospholipids surrounding a gas core made of fluorocarbons – gases of very high molecular weight which are already used in the clinic.
The active drug part can sit within the shell, inside another layer of liquid, or tagged onto the outside of the shell.
The inert bubble is administered via injection. “Because it’s full of gas it’s squishy and compressible,” said Stride. “When we expose it to ultrasound that will break the shell and release the drug.”
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Stride told in-Pharmatechnologist.com the bubble technology addresses bioavailability and unwanted side effects.
While scientists around the world are researching other types of stimuli-responsive drug delivery, “the good thing about ultrasound is it helps push the drug into the tissue – often the cells you’re trying to get at are nowhere near the [surface of the] tumour.”
The method can even magnetise the bubbles so they accumulate at the target site.
The bubbles last less than ten minutes in the bloodstream before breaking down, so the time between administration and ultrasound activation is very short.
Stride told us the bubble delivery technique could be especially helpful in rescuing four types of drug:
- Oncolytic viruses (viruses engineered to attack cancer cells)
- Antibody drug conjugates
- Small interfering RNA, and
- A novel type of radiopharmaceutical being developed by a group in Oxford.
So far the team has had success with the delivery system in mouse models. A clinical study at the University of Oxford is currently investigating using an existing drug in combination with ultrasound but without the bubble technology, and the team has applied for a second clinical trial involving bubbles and no ultrasound. Stride said she hopes the two can be combined in a human study within five years.
The programme has received around £10m ($15m) in funding from the government and pharma and is developing the technique through the Oxford Centre for Drug Delivery Devices.