PhD thesis provides new knowledge about oral delivery of biological drugs
28 september 2022
Biological drugs have an increasingly important function in healthcare, but despite numerous years of research, physicians often lack effective methods to give them as tablets. In a current PhD thesis, Staffan Berg presents new knowledge about how permeation enhancers and correct release profile can increase the absorption of biological drugs in the blood when delivered orally.
Today, every third new medicine is a so-called biological drug which originates from living sources, for example cells or tissue. Biological drugs have enabled treatment of previously incurable diseases, but due to their instability in the gastrointestinal tract they can seldom be administered as tablets or capsules. Therefore, a vast majority of biological drugs must be injected. In a current PhD thesis at Uppsala University, analyses of how the addition of permeation enhancers can increase the absorption of biological drugs in the gastrointestinal tract are now presented.
“Many biological drugs break down before they even reach the small intestine when administered orally. Due to size and polarity, they also have difficulties penetrating the intestinal mucosa and enter blood circulation. In my thesis, I analyse how increasing concentrations of sodium caprate, a frequently used permeation enhancer, affect the absorption of various model substances in rats,” says Staffan Berg, PhD student at the Department of Pharmacy.
The study shows that the local dose of sodium caprate delivered to the rat's small intestine has a large impact on the amount of drug that is absorbed. For several substances, uptake increases both initially and over time. For one substance, absorption rose after a while, but then continued for so long that the total absorption increased. The results illuminate the need for an informed choice of slow or fast release profile for each specific biological drug.
“We also studied solid drug preparations in pigs and dogs, and saw that dosage forms that release biological drugs and absorption enhancers in a limited part of the small intestine provide more reliable absorption than a solution and ordinary enterocoated tablets. In short, our results confirm the high potential of biological drugs also when administered orally, but that added enhancers do not provide general effects. Each combination of drug and permeation enhancer must be identified individually,” states Staffan Berg.
Staffan Berg has completed his doctoral studies within the framework of SweDeliver, a national research and competence center with a focus on drug delivery. With its academic hub at Uppsala University's Faculty of Pharmacy, SweDeliver unite fifteen selected pharmaceutical companies in different countries, among them AstraZeneca R&D in Gothenburg, which has formed the geographical base for Staffan Berg's work.
“Being part of SweDeliver continuously opens up new contact areas. During my visits to Uppsala and also online, I interact with researchers, postdocs and doctoral students at the Faculty of Pharmacy. Furthermore, close to 2,400 people work at AstraZeneca, many of whom show interest and provide important input to my research. In addition, it gives me access to state-of-the-art facilities, so for me, SweDeliver is adding extremely significant values.”
- Staffan Berg defends his thesis at BMC, hall A1:111a, Husargatan 3, Friday 30 September, at 09.15.
- The dissertation can also be seen online via Zoom. Connect via online via Zoom: : https://uu-se.zoom.us/j/62314206510.