Posted by HPβCD has also been investigated as an active pharmaceutical ingredient (API) for the prospective treatment of ischemic stroke. We previously demonstrated that repeated administration of HPβCD in young adult and aged mouse models attenuates immune cell infiltration and lipid droplet accumulation in infarcts and improves recovery at transcriptional and functional levels 7 weeks after ischemic stroke [1]. Furthermore, it was determined that HPβCD induces liver X receptor (LXR)-mediated transcriptional reprogramming in mouse stroke infarcts – a mechanism that aligns with the HPβCD-induced activation of LXR target genes observed in models of atherosclerotic plaque.
However, the efficacy of HPβCD as a treatment for ischemic stroke is dependent on its ability to penetrate ischemic brain tissue, a process influenced by dynamic alterations in BBB integrity and tissue composition over time [2]. The present study aimed to (1) assess the penetration and distribution of FITC-HPβCD within acute and subacute stroke infarcts, which are sites of persisting BBB impairment, and (2) validate the accumulation of FITC-HPβCD in previously identified target organs, including the kidneys, liver, and spleen. Using advanced imaging and analytical techniques, FITC-HPβCD delivery was studied to ischemic brain and peripheral tissues in aged (15-month-old) male mice subjected to stroke induced by distal middle cerebral artery occlusion 24 h or 1 week prior to subcutaneous administration of FITC-HPβCD.
The observed pharmacokinetic profile, characterized by renal excretion as the primary route of elimination and selective accumulation in infarcted brain regions with compromised BBB integrity, underscores its capacity to facilitate the clearance of cholesterol and other lipid byproducts resulting from myelin and cellular membrane degradation after ischemic stroke. Combined with its well-established safety profile, these results provide a strong rationale for further investigation into the therapeutic applications of HPβCD.
1 Becktel DA, et al. Repeated administration of 2-Hydroxypropyl-β-Cyclodextrin (HPβCD) attenuates the chronic inflammatory response to experimental stroke. J Neurosci. Jan. 2022;42(2):325–48. https://doi.org/10.1523/JNEUROSCI.0933-21.2021.
2 Becktel, D.A., Le, E.H., Frye, J.B. et al. 2-Hydroxypropyl-β-cyclodextrin accesses acute and subacute infarcts in a mouse model of ischemic stroke. Fluids Barriers CNS 23, 32 (2026). https://doi.org/10.1186/s12987-026-00767-9