Multivesicular liposomes containing cytarabine for slow-release Sc administration

Area of Science:

• Pharmacology
• Drug Delivery Systems
• Oncology

Background:

• Cytarabine is a chemotherapy drug used to treat leukemia.
• Rapid clearance of free cytarabine limits its therapeutic efficacy.
• Novel drug delivery systems are needed to improve cytarabine's pharmacokinetic profile.

Purpose of the Study:

• To evaluate the release kinetics of cytarabine encapsulated in multivesicular liposomes (MVLs).
• To assess the efficacy of a single subcutaneous dose of liposomal cytarabine in a murine leukemia model.

Main Methods:

• Subcutaneous administration of cytarabine-loaded MVLs to BDF1 mice.
• Measurement of drug release half-life in skin.
• Treatment of L1210 leukemia-bearing mice with a single subcutaneous dose of liposomal cytarabine.
• Monitoring long-term survival rates.

Main Results:

• Encapsulated cytarabine exhibited a prolonged skin half-life of 4 days, compared to 10 minutes for the free drug.
• A single subcutaneous dose of liposomal cytarabine resulted in long-term survivors across a broad dose range.
• The treatment was often curative for mice with systemic L1210 leukemia.

Conclusions:

• Multivesicular liposomes provide a sustained release of cytarabine from the skin.
• Single-dose subcutaneous administration of liposomal cytarabine is a potentially curative strategy for systemic leukemia.
• This liposomal formulation enhances the therapeutic potential of cytarabine.