Seen under the microscope, they look like gems, the so-called antibubbles that Rabia Zia (39) made during her innovative PhD research at the Department of Pharmaceutical Sciences at Utrecht University. The photos in her thesis show two or three small bubbles filled with liquid, ingeniously packed within an enveloping larger bubble filled with air. Beautiful to see. But Zia was not concerned about beauty.
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Rabia Zia investigated antibubbles as a new way to deliver medicine. The idea is that the medicine is safely contained in the inner small bubbles and is only released where it is needed. That would give it a significant advantage over existing drinks, pills and capsules. “The shell of air in the antibubbles serves as a protective barrier, allowing the drug to safely pass through the gastrointestinal tract. This prevents premature drug release and at the same time allows the location of release to be controlled,” says Zia via video link from Zurich.
“Antibubbles could prove useful in delivering medicines against local inflammation in the intestine, such as ulcerative colitis, Crohn’s disease and intestinal tuberculosis. But this could also provide a way to treat locally for stomach ulcers or intestinal tumors.”
Pioneering work
Zia’s PhD research was pioneering work: no one had ever done this before. She conducted experiments in the laboratory, simulating different environments in the gastrointestinal tract to see how the medicine packaged in anti-bubbles held up.
Making anti-bubbles starts with an emulsion of water in volatile oil, Zia explains. The silica nanoparticles she adds form a sturdy shell around the water droplets in the oil. She then reintroduces that emulsion into water, creating a water-oil-water emulsion. This is freeze-dried, which removes the water and oil. A powder remains. You can make anti-bubbles from this through rehydration; a water-air-water structure is then created.
During her PhD period, Rabia Zia regularly commuted between Utrecht and her home in the city of Al Ain in the United Arab Emirates. She had agreed with her supervisor that she could do part of her research at the university in Al Ain. She wanted to be with her family, but occasionally had to do tests in the lab in Utrecht. “Traveling back and forth was difficult,” says Zia, “but the hardest part was finding a temporary home in Utrecht every time. I was there for a few months and then not again.”
How Rabia Zia ended up in the Netherlands as a Pakistani for her PhD research is a long story, which she likes to tell. “It started about ten years ago, when I lived with my husband Akmal in the Netherlands for a year. He was doing his final year of PhD research at the University of Wageningen. He is a food technologist specialized in emulsions. And I had just graduated in pharmacy.”
“I was deeply inspired by the research environment he had around him. At that time, the idea of pursuing a PhD myself took root. But I then put the dream aside because I was pregnant with my first child. And shortly after that, life continued as normal. In 2018, we moved to the United Arab Emirates where Akmal got a job as an associate professor in the department of nutritional sciences. That’s when I was blessed with my other two children.”
However, in all those years, Zia’s desire to obtain a PhD had never disappeared. “When my children went to school, I decided that this was the time to pursue my long-cherished goal. But unfortunately there was no university in the United Arab Emirates that offered a PhD in pharmacy at the time. So I started looking for a supervisor in the Netherlands, because my husband also wanted me to do it here. We were familiar with the environment, the people and the entire culture. A nice place to be, very safe and I felt connected here.”
Quite a challenge
Zia eventually found a PhD position with pharmacochemist René van Nostrum at Utrecht University. “He was amazed at my determination to start a PhD while raising three children. And yes, that is quite a challenge. Fortunately, I was allowed to do part of my research in the United Arab Emirates, so I could still stay close to my family as much as possible.”
Van Nostrum and her co-supervisor Albert Poortinga from Eindhoven University of Technology, who had already laid a foundation with research into antibubbles, visited her in the United Arab Emirates at the start of the project. The start-up phase was difficult, says Zia. There was no research on which she could build, she had to invent everything herself. But when she got the first results and noticed that scientific journals were happy to publish her articles – “the word antibubbles fascinated them, I think” – she became more and more confident.
The first time I had to give a presentation I was literally shaking. But everyone was so supportive, which really made me feel like myself
The Dutch have stolen her heart: “There is something that is in line with my nature, that I really feel at ease with the Dutch. They are very direct and that makes communication very easy. I also felt very supported at university. The first time I had to give a presentation I was literally shaking. But everyone was so supportive, which made me really feel like myself.”
Zia realizes that actually administering medication with antibubbles is still a long way off. Her research was one proof of concept. All tests were in vitro, simulations of the conditions in the intestinal tract to see how the anti-bubbles would behave. Zia filled antibubbles with drugs and exposed them to digestive enzymes, a low pH that mimicked the action of stomach acid, and finally bile salts, which are released in the small intestine.
Send medication delivery
She showed that by changing the composition of the nanoparticles that keep the antibubbles stable, it is possible to control the release of drug in the gastrointestinal tract. For example, by incorporating calcium carbonate particles into it, the anti-bubbles in the stomach burst due to the action of stomach acid.
According to Zia, who received her PhD at the beginning of November, there is still a lot of work to be done before the first animal research with antibubbles can be carried out. “For example, we should still test it in ‘gut-on-a-chip’ models, where we examine how the local immune system responds to these anti-bubbles. We currently still use silica particles on the surfaces, but I would also like to investigate whether they can be replaced by biodegradable particles because they are probably better tolerated.”
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The limit Zia encountered in her research was the effect of bile salts. “They always ended up destroying the anti-bubbles.” She would ideally like to find a way to keep the antibubbles intact in the large intestine where they would burst, for example, by enzymes of intestinal bacteria, releasing the medicine.
Another wish on her research list is reduction in size. “We produced antibubbles of about 20 to 30 micrometers, which is still quite a large size. With that, we can expect a local targeted release. But if we really want them to be absorbed by the intestinal epithelium, many other things have to happen.”
Who is
Rabia Zia?
- Born
- In 1986, in Karachi, Pakistan
- Lives in
- Al Ain, United Arab Emirates
- Favorite sport
- “I like swimming. And I also want to start lifting weights again to stay in shape.”
- Favorite Dutch food
- “Peanut butter! That really is a great invention.”
- Dreams of
- “Start your own start-up, preferably in the Netherlands. My co-promoter, Albert Poortinga with his company Bether Encapsulates, is my role model. I would like that too.”
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