Polyelectrolyte complex optimization for macrophage delivery of redox enzyme nanoparticles

Yuling Zhao, Matthew J. Haney, Natalia L. Klyachko, Shu Li, Stephanie L. Booth, Sheila M. Higginbotham, Jocelyn Jones, Matthew C. Zimmerman, R. Lee Mosley, Alexander V. Kabanov, Howard E. Gendelman, Elena V. Batrakova

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Background: We posit that cell-mediated drug delivery can improve transport of therapeutic enzymes to the brain and decrease inflammation and neurodegeneration seen during Parkinsons disease. Our prior works demonstrated that macrophages loaded with nanoformulated catalase ('nanozyme) then parenterally injected protect the nigrostriatum in a murine model of Parkinsons disease. Packaging of catalase into block ionomer complex with a synthetic polyelectrolyte block copolymer precludes enzyme degradation in macrophages. Methods: We examined relationships between the composition and structure of block ionomer complexes with a range of block copolymers, their physicochemical characteristics, and loading, release and catalase enzymatic activity in bone marrow-derived macrophages. Results: Formation of block ionomer complexes resulted in improved aggregation stability. Block ionomer complexes with -polylysine and poly(L-glutamic acid)-poly(ethylene glycol) demonstrated the least cytotoxicity and high loading and release rates. However, these formulations did not efficiently protect catalase inside macrophages. Conclusion: Nanozymes with polyethyleneimine- and poly(L-lysine) 10-poly(ethylene glycol) provided the best protection of enzymatic activity for cell-mediated drug delivery.

Original languageEnglish (US)
Pages (from-to)25-42
Number of pages18
JournalNanomedicine
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2011

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Keywords

  • Parkinson's disease
  • blood-brain barrier
  • catalase
  • cell-mediated drug delivery
  • nanozyme
  • neuroinflammation

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Materials Science(all)

Cite this

Zhao, Y., Haney, M. J., Klyachko, N. L., Li, S., Booth, S. L., Higginbotham, S. M., Jones, J., Zimmerman, M. C., Mosley, R. L., Kabanov, A. V., Gendelman, H. E., & Batrakova, E. V. (2011). Polyelectrolyte complex optimization for macrophage delivery of redox enzyme nanoparticles. Nanomedicine, 6(1), 25-42. https://doi.org/10.2217/nnm.10.129