Drug Delivery of Biopharmaceuticals Into and Across Biobarriers

Professor Hanne Mørck Nielsen, Department of Pharmacy, University of Copenhagen

Approaches to facilitate delivery of drugs into and across biological barriers will be presented with a focus on the interplay between formulation design, drug delivery system characteristics and administration site.

The talk will comprise a presentation of selected drug delivery systems; their design, formulation, characterization and delivery potential. Specifically, focus will be on our efforts to formulate drug delivery systems for oral peptide delivery in relation to work ongoing in the Biodelivery Center (NNF Grand Challenge interdisciplinary project) as well as on delivery of antimicrobials into biofilm. We develop and apply a variety of orthogonal methods and models to assess and understand crucial aspects of the delivery process, such as the mechanisms of action(s) of e.g. cell-penetrating/membrane-interacting peptides as permeation enhancers.

The drug delivery systems are characterized as nanoparticles and/or systems with nanoscale properties that are important for their function. Also, we address nanoscale observations in biological matrices such as biofilm, mucus and epithelium.

Host: Associate Professor Ken Howard

References:

• Diedrichsen, R.G., Harloff-Helleberg, S., Werner, U., Besenius, M., Kristensen, M., Nielsen, H.M. Revealing the importance of carrier-cargo association in delivery of insulin and lipidated insulin, J Control Release, 338 (2021) 8-21, https://doi.org/10.1016/j.jconrel.2021.07.030
• Streck, S., Bohr, S.S.-R., Birch, D., Rades, T., Hatzakis, N.S., McDowell, A., Nielsen, H.M. Interactions of cell-penetrating peptide-modified polymeric nanoparticles with the nano-bio interface evaluated using single particle tracking, ACS Appl Bio Mater 4 (2021) 3155-3165, https://doi.org/10.1021/acsabm.0c01563
• Wan, F., Bohr, S.S.-R., Kłodzińska, S.N., Jumaa, H., Nylander, T., Thygesen, M.B., Sørensen, K.K., Jensen, K.J., Sternberg, C., Hatzakis, N., Nielsen, H.M. Ultra-small TPGS-PLGA hybrid nanoparticles for site-specific delivery of antibiotics into pseudomonas aeruginosa in biofilms in lungs. ACS Appl. Mater. Inter. 12 (2020) 380-389, https://doi.org/10.1021/acsami.9b19644.
• Rovira, D.S., Nielsen, H.M., Taboryski, R., Bunea, A.-I. 3D printed scaffolds for biomimetic cell membranes, Materials & Design, 201 (2021) 109486, https://doi.org/10.1016/j.matdes.2021.109486
• Hedegaard, S.F., Bruhn, D.S., Khandelia, H., Cárdenas, M., Nielsen, H.M. Shuffled lipidation pattern and degree of lipidation determines the membrane interaction behavior of a linear cationic membrane-active peptide. J. Surface Colloid. Sci. 578 (2020) 584-597, https://doi.org/10.1016/j.jcis.2020.05.121