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Chitosan nanoparticle-based neuronal membrane sealing and neuroprotection following acrolein-induced cell injury

Youngnam Cho1, Riyi Shi12 and Richard Ben Borgens12*

  • * Corresponding author: Richard Ben Borgens cpr@purdue.edu

  • † Equal contributors

Author Affiliations

1 Center for Paralysis Research, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA

2 Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA

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Journal of Biological Engineering 2010, 4:2  doi:10.1186/1754-1611-4-2

Published: 29 January 2010

Abstract

Background

The highly reactive aldehyde acrolein is a very potent endogenous toxin with a long half-life. Acrolein is produced within cells after insult, and is a central player in slow and progressive "secondary injury" cascades. Indeed, acrolein-biomolecule complexes formed by cross-linking with proteins and DNA are associated with a number of pathologies, especially central nervous system (CNS) trauma and neurodegenerative diseases. Hydralazine is capable of inhibiting or reducing acrolein-induced damage. However, since hydralazine's principle activity is to reduce blood pressure as a common anti-hypertension drug, the possible problems encountered when applied to hypotensive trauma victims have led us to explore alternative approaches. This study aims to evaluate such an alternative - a chitosan nanoparticle-based therapeutic system.

Results

Hydralazine-loaded chitosan nanoparticles were prepared using different types of polyanions and characterized for particle size, morphology, zeta potential value, and the efficiency of hydralazine entrapment and release. Hydralazine-loaded chitosan nanoparticles ranged in size from 300 nm to 350 nm in diameter, and with a tunable, or adjustable, surface charge.

Conclusions

We evaluated the utility of chitosan nanoparticles with an in-vitro model of acrolein-mediated cell injury using PC -12 cells. The particles effectively, and statistically, reduced damage to membrane integrity, secondary oxidative stress, and lipid peroxidation. This study suggests that a chitosan nanoparticle-based therapy to interfere with "secondary" injury may be possible.