Triggering liposomal drug release with a lysosomotropic agent.

Area of Science:

• Pharmacology
• Nanotechnology
• Oncology

Background:

• Drug release from liposomes into the cytoplasm is crucial for anticancer drug efficacy.
• Lysosomotropic agents like chloroquine can enhance the cytotoxicity of basic anticancer drugs.

Purpose of the Study:

• To investigate the mechanism by which chloroquine triggers drug release from liposomes.
• To evaluate the potential of chloroquine in combination therapy for solid tumors.

Main Methods:

• Daunorubicin was loaded into folate-targeted liposomes using an ammonium sulfate gradient.
• In vitro release studies, cytotoxicity assays, and confocal microscopy were performed.
• Intraliposomal pH changes were measured using HPTS-loaded liposomes.

Main Results:

• Chloroquine triggered the immediate release of approximately 11% of daunorubicin from liposomes in vitro.
• Chloroquine enhanced the in vitro cytotoxicity of liposomal daunorubicin against L1210JF(FR+) cells.
• Chloroquine increased intraliposomal pH but not above 5.5, suggesting ion exchange and pH rise as release mechanisms.
• In vivo studies on a murine solid tumor model confirmed chloroquine-induced drug release from liposomes.

Conclusions:

• Chloroquine effectively triggers the release of daunorubicin from liposomes through ion exchange and pH elevation.
• The combination of chloroquine with liposomal anticancer drugs holds promise for improving therapeutic outcomes in solid tumors.