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

E Barcia, A Salama, A Fernández-Carballido, S Negro

Journal: Journal of drug targeting 2012;19(8):637-46

PMID: 20945972

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

H(2)O(2) (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.

Address: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain. [email protected]

DOI: 10.3109/1061186X.2010.523789