Posted by Acute myeloid leukaemia (AML), accounts for 30 % of adult leukaemia cases, predominantly affects individuals over 60. The standard “7 + 3” intensive chemotherapy regimen is unsuitable for many elderly patients, contributing to AML’s poor prognosis. While progress in drug therapies has been made, breakthroughs remain limited, indication-specific, and slow to expand. Drug repurposing offers a faster route to therapy development, while nanocarrier encapsulation broadens the scope of viable drug candidates.
Chlorpromazine (CPZ) is an antipsychotic which has been identified as a potential anti-leukaemic agent. Due to its ability to cross the blood-brain barrier, it is likely to cause central nervous system (CNS) effects. The drug-in-cyclodextrin-in-liposome (DCL) nanocarrier platform enables the formulation of CPZ encapsulated with cyclodextrins (CDs) such as HP-γ-CD, SBE-β-CD, and Sugammadex.
The CD/CPZ formulations were equally, or more efficient than free CPZ in inducing AML cell death. Uptake of the DCL in AML cells quickly reached saturation, with minimal differences among formulations, except for SBE-β-CD. When injected intravenously in zebrafish larvae the different DCLs did not differ in biodistribution, and no brain accumulation was observed at two days post-injection. These DCL-based CPZ formulations maintain anti-leukaemic activity, avoid CNS accumulation, and allow drug availability adjustments based on the included CD.
Edvin Tang Gundersen, Zhiqiang Wang, Jan-Lukas Førde, Eric Larquet, Reidun Æsøy, Hugo Roussel, Lou Tosi, Gillian Barratt, Lars Herfindal, François-Xavier Legrand (2025) Repurposing chlorpromazine for anti-leukaemic therapy with the drug-in-cyclodextrin-in-liposome nanocarrier platform. Carbohydrate Polymers 123478. https://doi.org/10.1016/j.carbpol.2025.123478.