2026-04-17T23:03:30Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4631982024-11-04T04:19:15Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Al-Ahmady, Zahraa S. author Dickie, Ben R. author Aldred, Isabelle author Jasim, Dhifaf A. author Barrington, Jack author Haley, Michael J author Lemarchand, Eloise author Coutts, Graham author Kaur, Satinderdeep author Bates, Jessica author Curran, Sarah author Goddard, Ruth author Walker, Megan author Parry-jones, Adrian author Kostarelos, Kostas author Allan, Stuart M. author 2022 Haemorrhagic stroke represents a significant public health burden, yet our knowledge and ability to treat this type of stroke are lacking. Previously we showed that we can target ischaemic-stroke lesions by selective translocation of lipid nanoparticles through the site of blood-brain barrier (BBB) disruption. The data we presented in this study provide compelling evidence that haemorrhagic stroke in mice induces BBB injury that mimics key features of the human pathology and, more importantly, provides a gate for entry of lipid nanoparticles-based therapeutics selectively to the bleeding site. Methods: Haemorrhagic stroke was induced in mice by intra-striatal collagenase injection. lipid nanoparticles were injected intravenously at 3 h, 24 h & 48 h post-haemorrhagic stroke and accumulation in the brain studied using in-vivo optical imaging and histology. BBB integrity, brain water content and iron accumulation were characterised using dynamic contrast-enhanced MRI, quantitative T mapping, and gradient echo MRI. Results: Using in-vivo SPECT/CT imaging and optical imaging revealed biphasic lipid nanoparticles entry into the bleeding site, with an early phase of increased uptake at 3-24 h post-haemorrhagic stroke, followed by a second phase at 48-72 h. Lipid nanoparticles entry into the brain post-haemorrhage showed an identical entry pattern to the trans-BBB leakage rate (K trans [min -1 ]) of Gd-DOTA, a biomarker for BBB disruption, measured using dynamic contrast-enhanced MRI. Discussion: Our findings suggest that selective accumulation of liposomes into the lesion site is linked to a biphasic pattern of BBB hyper-permeability. This approach provides a unique opportunity to selectively and efficiently deliver therapeutic molecules across the BBB, an approach that has not been utilised for haemorrhagic stroke therapy and is not achievable using free small drug molecules. http://hdl.handle.net/2072/463198 Liposomes Blood-brain barrier Drug delivery Haemorrhagic stroke Lipid nanoparticles Selective brain entry of lipid nanoparticles in haemorrhagic stroke is linked to biphasic blood-brain barrier disruption