Liposomal squalenoyl-gemcitabine: formulation, characterization and anticancer activity evaluation

Area of Science:

• Oncology
• Drug Delivery
• Nanotechnology

Background:

• Gemcitabine is a widely used anticancer nucleoside analogue.
• Developing effective drug delivery systems is crucial for enhancing chemotherapy efficacy and reducing side effects.
• Prodrug strategies can improve the pharmacokinetic and pharmacodynamic properties of existing drugs.

Purpose of the Study:

• To investigate the feasibility of encapsulating a novel gemcitabine prodrug, GemSQ (squalene-gemcitabine), into liposomes.
• To evaluate the in vivo anticancer activity of liposomal GemSQ formulations (PEGylated and non-PEGylated) in a leukemia model.
• To compare the efficacy of liposomal GemSQ with free gemcitabine.

Main Methods:

• Synthesis of the gemcitabine-squalene prodrug (GemSQ).
• Encapsulation of GemSQ into liposomes, including PEGylated and non-PEGylated variants.
• In vivo evaluation of anticancer activity using a subcutaneous L1210wt leukemia mouse model.

Main Results:

• Successful encapsulation of GemSQ into liposomes was achieved.
• Liposomal GemSQ formulations exhibited significant in vivo anticancer activity against L1210wt leukemia.
• The efficacy of liposomal GemSQ was superior to that of free gemcitabine in the tested model.

Conclusions:

• Liposomal GemSQ represents a viable and effective drug delivery system for gemcitabine.
• This approach holds potential for improving the treatment of various tumors sensitive to gemcitabine.
• Further research into liposomal GemSQ could lead to advanced cancer therapies.