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

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      1 , 1 , 2 , 1 , 2 ,
      Journal of Biological Engineering
      BioMed Central

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          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.

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          Most cited references46

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          Small-scale systems for in vivo drug delivery.

          Recent developments in the application of micro- and nanosystems for drug administration include a diverse range of new materials and methods. New approaches include the on-demand activation of molecular interactions, novel diffusion-controlled delivery devices, nanostructured 'smart' surfaces and materials, and prospects for coupling drug delivery to sensors and implants. Micro- and nanotechnologies are enabling the design of novel methods such as radio-frequency addressing of individual molecules or the suppression of immune response to a release device. Current challenges include the need to balance the small scale of the devices with the quantities of drugs that are clinically necessary, the requirement for more stable sensor platforms, and the development of methods to evaluate these new materials and devices for safety and efficacy.
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            Liposomes in drug delivery: Progress and limitations

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              Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers

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                Author and article information

                Journal
                J Biol Eng
                Journal of Biological Engineering
                BioMed Central
                1754-1611
                2010
                29 January 2010
                : 4
                : 2
                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
                Article
                1754-1611-4-2
                10.1186/1754-1611-4-2
                2824642
                20205817
                24ca03f9-50b8-4438-825b-fd4cbdc62493
                Copyright ©2010 Cho et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 October 2009
                : 29 January 2010
                Categories
                Research

                Biotechnology
                Biotechnology

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