Parenteral drug delivery work package – Home to a diversity of high-quality research

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Parenteral drug delivery is a widely used route of administration. Given by injection, the drug reaches the target organ without crossing biological barriers. Significant progress has also been made in providing a sustained release of the drug in a predictable manner. This method is particularly useful for active pharmaceutical substances with narrow therapeutic index and poor bioavailability. However, substantial scientific challenges remain before the parenteral route can reach its full potential.

At the Parenteral drug delivery Work package, pharmaceutical companies and the Faculty of Pharmacy in close cooperation aim to develop novel formulations and improved delivery systems for subcutaneous drug administration. Former bilateral constellations have been replaced with an extensive and interdisciplinary network, characterised by openness and trust. The research conducted addresses everyone's challenges and benefits everyone's interests.

“By ensuring balance and equality in each constellation, we have been able to reach consensus in all our operations. We have successfully defined our common goals, focusing on the development of novel methods for evaluating the behaviour of potential pharmaceuticals administered subcutaneously. Early on, we strengthened our research environment by recruiting a number of very promising young researchers who today play important roles in our scientific progress,” says Per Hansson, Work package leader and Professor of Physical Chemistry.

Being part of SweDeliver’s predecessor: the Swedish Drug Delivery Forum (SDDF), provided the team with financial resources that has enabled long-term investments in advanced technical equipment. Today, the research environment at the Uppsala Biomedical Centre has access to Small-Angle X-ray Scattering, SAXS, an efficient and economical method to determine the structure of drug formulations and biomacromolecules in solution.

“After years of time-consuming travels to limited time slots at large-scale research facilities, we can now perform continuous operations in our own premises. This adds considerable value that has become even more obvious during present corona-related restrictions, and has also proven to be a key factor in the scientific progress made in a number of studies connected with our work package,” Per Hansson continues.

(Image removed) In the projectAmphiphilic drugs in microgels, PhD student Yassir Al-Tikriti explores the possibilities of utilising polyectrolyte microgels as carriers of amphiphilic drug molecules, the latter being a group of active substances frequently used in cancer therapies and as antidepressants. This task requires determining the basic principles governing the drug loading and release properties of the microgel. In a parallel project, PhD student Vahid Forooqi Motlaq studies the interactions and self-assembly in mixtures of different amphiphilic drug molecules and lipid bilayers.

“We combine powerful experimental methods and theoretical modelling approaches to attain information about the amphiphilic properties of small drug molecules. Our aim is to provide models relevant to the development of novel release systems for amphiphilic drugs, and a better fundamental understanding of self-assembly structures and release mechanisms in drug delivery systems,” Yassir Al-Tikriti states.

In the projectNovel in vitro models for subcutaneous administration of drugs, postdoc Agnes Rodler has constructed a physiologically relevant synthetic model of the extracellular matrix, making it possible to mimic the behaviour of drug formulations injected under the human skin. Research is also underway on how active pharmaceutical ingredients and excipients in subcutaneously administered drug formulations interact with the components in the matrix.

“Since fat tissue is poorly perfused, the transport rate is low and the drug may suffer degradation or aggregation before reaching the circulatory system, especially if the drug is a protein. This is a challenge outlined by a number of our SweDeliver’s industrial partners, and with the design phase now complete and our model up and running, I hope that the matrix will enable more precise predictions of the fate that awaits potential drug formulations after administration in the body,” Agnes Rodler says.

For Per Hansson's research group, SweDeliver has affected their daily efforts in several dimensions. The proportion of international members has increased significantly. The mixture of diverse experiences and perspectives creates both synergies and new ideas. The team participates in extensive and exciting projects in close connection with the pharmaceutical industry. At the centre of action is the meticulously assembled group of young PhDs and postdocs who are now laying the foundations for their future careers in the field of life science and drug delivery.

“Access to qualified employees and expertise in drug delivery is crucial to a pharmaceutical company like AstraZeneca and this was certainly a contributing factor in our involvement in the forum. Today we are an integrated part of an ecosystem where a wide range of talented researchers move between companies and academia. It is a considerable shift of gear, likely to generate competence, companies and jobs for a long time to come,” says Mats Berglund, Vice President of ISEL, AstraZeneca and Chair of the Swedish Drug Delivery Forum.

At this point, the Parenteral Drug Delivery work package is home to a diversity of high-quality research. This new meeting place has become a melting pot for interdisciplinary talks, innovative thoughts and a shared desire to accelerate the process from idea to market-ready product. Here, novel methods are being developed and inspired initiatives shaped. SweDeliver has become a natural extension from SDDF, here additional challenges are being explored, new partners are introduced and old borders are crossed.

“We are now preparing to utilise a number of our experimental models in the development of new drugs. In connection with this, Sara Mangsbo, a renowned researcher in immunology, will join our organisation to study how a range of peptides aggregate in the human body and determine their potential to aid in the fight against cancer. In addition, we are happy to welcome a number of Scandinavian companies, allowing us to exchange knowledge and getting an overview of the resources we can gather for future international collaborations, hence adding another dimension to our forum,” Per Hansson concludes.

More information

Read about  Projects in the Parenteral drug delivery Work package (Link removed)

Contact

Work package leaders
Professor Per Hansson, Department of Medicinal Chemistry, Uppsala University
Doctor Susanna Abrahmsén Alami, AstraZeneca

text: Magnus Alsne, photo: Mikael Wallerstedt