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Nanomedicine (Lond). 2010 Apr;5(3):379-96. doi: 10.2217/nnm.10.7.

Macrophage delivery of therapeutic nanozymes in a murine model of Parkinson's disease.

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1
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.

Abstract

BACKGROUND:

Parkinson's disease is a common progressive neurodegenerative disorder associated with profound nigrostriatal degeneration. Regrettably, no therapies are currently available that can attenuate disease progression. To this end, we developed a cell-based nanoformulation delivery system using the antioxidant enzyme catalase to attenuate neuroinflammatory processes linked to neuronal death.

METHODS:

Nanoformulated catalase was obtained by coupling catalase to a synthetic polyelectrolyte of opposite charge, leading to the formation of a polyion complex micelle. The nanozyme was loaded into bone marrow macrophages and its transport to the substantia nigra pars compacta was evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice.

RESULTS:

Therapeutic efficacy of bone marrow macrophages loaded with nanozyme was confirmed by twofold reductions in microgliosis as measured by CD11b expression. A twofold increase in tyrosine hydroxylase-expressing dopaminergic neurons was detected in nanozyme-treated compared with untreated MPTP-intoxicated mice. Neuronal survival was confirmed by magnetic resonance spectroscopic imaging. Bone marrow macrophage-loaded catalase showed sustained release of the enzyme in plasma.

CONCLUSION:

These data support the importance of macrophage-based nanozyme carriage for Parkinson's disease therapies.

PMID:
20394532
PMCID:
PMC2880389
DOI:
10.2217/nnm.10.7
[Indexed for MEDLINE]
Free PMC Article

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