Repurposing chlorpromazine for anti-leukaemic therapy by nanoparticle encapsulation

Area of Science:

• Nanomedicine
• Pharmacology
• Oncology

Background:

• Acute myeloid leukaemia (AML) treatment faces challenges with poor prognosis and survival rates, necessitating novel therapeutic strategies.
• Drug repurposing and nanocarrier encapsulation offer promising avenues for developing new AML therapies.
• Chlorpromazine (CPZ), an antipsychotic drug, has emerged as a potential candidate for AML treatment.

Purpose of the Study:

• To develop PEGylated PLGA nanoparticles loaded with chlorpromazine (CPZ) for acute myeloid leukaemia (AML) therapy.
• To evaluate the physicochemical properties, drug release kinetics, and in vitro/in vivo efficacy of CPZ-loaded nanoparticles.
• To assess the potential of nanoencapsulation to mitigate CPZ's central nervous system side effects.

Main Methods:

• Utilized the emulsion-evaporation technique to create PEGylated PLGA nanoparticles encapsulating CPZ.
• Characterized nanoparticles using Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM).
• Assessed drug loading, in vitro drug release profiles, cytotoxicity against AML cells, and in vivo brain accumulation in zebrafish larvae.

Main Results:

• Developed spherical nanoparticles (150-300 nm) with a drug loading of at least 6.0% (w/w).
• Demonstrated sustained CPZ release over 24 hours after an initial burst release.
• CPZ-loaded nanoparticles exhibited comparable cytotoxicity to free CPZ against AML cells with slower action and showed no brain accumulation in zebrafish larvae.

Conclusions:

• Nanoencapsulation of CPZ in PEGylated PLGA nanoparticles successfully retains anti-AML activity.
• The developed nanocarrier system effectively prevents CPZ accumulation in the central nervous system.
• This approach holds potential for safer and more effective AML treatment by repurposing CPZ.