Development and In Vitro and In Vivo Evaluation of an Antineoplastic Copper(II) Compound (Casiopeina III-ia) Loaded in Nonionic Vesicles Using Quality by Design.

Abstract

In recent decades, the interest in metallodrugs as therapeutic agents has increased. Casiopeinas are copper-based compounds that have been evaluated in several tumor cell lines. Currently, casiopeina III-ia (CasIII-ia) is being evaluated in phase I clinical trials. The aim of the present work is to develop a niosome formulation containing CasIII-ia for intravenous administration through a quality-by-design (QbD) approach. Risk analysis was performed to identify the factors that may have an impact on CasIII-ia encapsulation. The developed nanoformulation optimized from the experimental design was characterized by spectroscopy, thermal analysis, and electronic microscopy. In vitro drug release showed a burst effect followed by a diffusion-dependent process. The niosomes showed physical stability for at least three months at 37 °C and 75% relative humidity. The in vitro test showed activity of the encapsulated CasIII-ia on a metastatic breast cancer cell line and the in vivo test of nanoencapsulated CasIII-ia maintained the activity of the free compound, but showed a diminished toxicity. Therefore, the optimal conditions obtained by QbD may improve the scaling-up process.

• Authors: Zenayda Aguilar-Jiménez, Mauricio González-Ballesteros, Silvia G Dávila-Manzanilla, Adrián Espinoza-Guillén, Lena Ruiz-Azuara
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 21 (Oct 22 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36361549 (Publication Type: Journal Article)

Chemical References

• (4,4-dimethyl-2,2-bipyridine)(acetylacetonate)copper(II)
• Copper
• Organometallic Compounds
• Antineoplastic Agents
• Liposomes

Topics

• Copper (chemistry)
• Organometallic Compounds (chemistry)
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Liposomes