The blood-brain barrier (BBB) is a major obstacle to treating several brain disorders. Focused ultrasound (FUS) in combination with intravascular microbubbles increases BBB permeability by opening tight junctions, creating endothelial cell openings, improving endocytosis and increasing transcytosis. Here we investigated whether combining FUS and microbubbles with transferrin receptor-targeting liposomes would result in enhanced delivery to the brain of post-natal rats compared with liposomes lacking the BBB-targeting moiety. For all animals, increased BBB permeability was observed after FUS treatment. A 40% increase in accumulation of transferrin receptor-targeting liposomes was observed in the FUS-treated hemisphere, whereas the isotype immunoglobulin G liposomes showed no increased accumulation. Confocal laser scanning microscopy of brain sections revealed that both types of liposomes were mainly observed in endothelial cells in the FUS-treated hemisphere. The results demonstrate that FUS and microbubble treatment combined with BBB-targeting liposomes could be a promising approach to enhance drug delivery to the brain.
|Journal||Ultrasound in Medicine and Biology|
|Publication status||Published - 2021|
Bibliographical noteFunding Information:
We thank Torben Moos, Aalborg University, for providing the OX26 antibody and Sofie Snipstad and Sigrid Berg for their technical support with the FUS instrumentation. MRI was performed at the MR Core Facility, Norwegian University of Science and Technology (NTNU). We acknowledge Deborah Hill for her technical assistance with the MRI. Housing of the animals was provided by the Comparative Medicine Core Facility (NTNU). Tissue sections were prepared by the Cellular and Molecular Imaging Core Facility (NTNU). We thank Astrid Bj?rk?y and the Centre for Advanced Microscopy at the Faculty of Natural Sciences (NTNU) for technical assistance with CLSM. Illustrations were created with BioRender.com. The project was internally funded by the Norwegian University of Science and Technology and the Technical University of Denmark. Thomas Lars Andresen acknowledges generous support from the Lundbeck Foundation Research Initiative on Brain Barriers and Drug Delivery ( www.ribbdd.dk; grant R155-2013-14113). The authors declare no competing interest.
- Blood–brain barrier disruption
- Transferrin receptor-targeting