Protective effects of clioquinol on human neuronal-like cells: a new formulation of clioquinol-loaded PLGA microspheres for Alzheimer’s disease

Abstract

Background: Clioquinol (CQ), a metal chelator, has gained renewed attention due to its ability to modulate metal homeostasis in neurodegenerative disorders such as Alzheimer’s disease.

Purpose: To investigate the protective effects of a wide range of concentrations of CQ on two human neuroblastoma cell lines (IMR-32 and SKN-AS) and to develop and characterize a new controlled release system of CQ consisting of biodegradable microspheres.

Results: H₂O₂ (400 μM) adequately induced death cell in IMR-32 and SKN-AS cell lines thereby resulting in a useful model for neuroprotective studies. CQ (20–50 μM) induced a potent and robust protective effect against peroxide-mediated oxidative stress in human neuronal-like cells (SKN-AS) determined by both MTT and flow cytometry (cell viability). These results were also confirmed by means of reactive oxygen species (ROS) production. Biodegradable poly(dl-lactic-co-glycolic acid) (PLGA) resomers assayed for microspheres preparation were PLGA-502 and PLGA-502H. Optimization by using an experimental design resulted in a formulation prepared with CQ (112 mg) and PLGA-502H (400 mg). With this formulation, mean encapsulation efficiency of 82.37% ± 6.67% and, zero-order release rate of 58 ± 3µg CQ/day/10 mg microspheres between Days 10 and 35 were obtained.

Conclusion: We have developed a promising formulation for the treatment of Alzheimer’s disease.

Keywords::

• Biodegradable polymer
• cell model
• IMR-32
• SKN-AS
• neuroprotection
• PLGA microspheres
• controlled drug delivery

Acknowledgements

The authors thank Dr. S. Ropero (Dpto Bioquímica y Biología Molecular, Universidad de Alcalá) for the donation of IMR-32 and SKN-AS cell lines. The authors thank I. Trabado from La Unidad de Cultivos de Células Humanas (Universidad de Alcalá), Centro de Microscopía Electrónica “Luis Bru” (CAI, UCM), and X-ray diffraction CAI (UCM), for their technical assistance.

Declaration of interest

This work was supported by research projects Santander-UCM (PR41/06-14951) and UCM-CAM (research group 910939). The authors report no declarations of interest.