HPβCD-Cu(DDC)2

HPβCD-Cu(DDC)2 is a novel drug delivery system consisting of an inclusion complex between 2-hydroxypropyl-β-cyclodextrin (HPβCD) and copper(II) diethyldithiocarbamate (Cu(DDC)2). The formulation was designed to address the practical insolubility of Cu(DDC)2 in water while maintaining its potent anticancer activity. HPβCD acts as a solubility enhancer and stabilizer, encapsulating Cu(DDC)2 within its hydrophobic cavity to create a stable, water-soluble complex. The mechanism of action involves inhibition of O6-methylguanine-DNA methyltransferase (MGMT) through the ubiquitin proteasome pathway, which is particularly relevant for treating glioblastoma and other chemoresistant cancers. The HPβCD carrier stabilizes Cu(DDC)2 and significantly improves drug delivery and bioactivity compared to free Cu(DDC)2. Studies demonstrate efficacy against patient-derived glioblastoma models and chemoresistant triple-negative breast cancer cell lines with IC50 values less than 200 nM. The formulation can be prepared by simple mixing at room temperature and maintains stability for 28 days without precipitation or crystallization. This represents a promising approach for anticancer applications, particularly in treating drug-resistant malignancies.

Other names

Hydroxypropyl-beta-cyclodextrin diethyldithiocarbamate copper II inclusion complexHPβCD-DDC-Cu complex2-Hydroxypropyl-β-cyclodextrin Cu(DDC)2 delivery system