Development of a copper-clioquinol formulation suitable for intravenous use

Area of Science:

• Pharmacology
• Nanotechnology
• Oncology

Background:

• Clioquinol (CQ), an antifungal, has shown anticancer properties but failed in clinical trials due to poor oral absorption.
• Copper complex of clioquinol (Cu(CQ)2) exhibits enhanced anticancer activity.
• Liposomal encapsulation offers a novel approach for intravenous delivery of drug complexes.

Purpose of the Study:

• To develop and evaluate a liposomal formulation of Cu(CQ)2 for intravenous administration.
• To assess the efficacy of liposomal Cu(CQ)2 alone and in combination with disulfiram (DSF) in preclinical cancer models.
• To investigate the potential of liposomal Cu(CQ)2 to enhance copper delivery to cancer cells.

Main Methods:

• Synthesized Cu(CQ)2 within 100-nm liposomes (1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol, 55:45).
• Evaluated therapeutic activity in subcutaneous glioblastoma and ovarian cancer models.
• Assessed in vitro copper delivery and combined effects with DSF.

Main Results:

• Liposomal Cu(CQ)2 formulation suitable for intravenous administration was successfully prepared.
• The formulation did not show significant therapeutic activity in glioblastoma or ovarian cancer models.
• In vitro studies indicated enhanced cellular copper levels and disulfiram activity, but this did not translate to significant in vivo tumor reduction.

Conclusions:

• Liposomal encapsulation enables intravenous delivery of Cu(CQ)2.
• The tested formulation was not efficacious as a monotherapy or in combination with DSF in preclinical cancer models.
• The methodology is applicable for developing other 8-hydroxyquinoline analogues with potentially improved potency.