Polyelectrolyte complex optimization for macrophage delivery of redox enzyme nanoparticles

聚电解质复合物优化用于巨噬细胞递送氧化还原酶纳米粒子

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作者: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

Background

We posit that cell-mediated drug delivery can improve transport of therapeutic enzymes to the brain and decrease inflammation and neurodegeneration seen during Parkinson's disease. Our prior works demonstrated that macrophages loaded with nanoformulated catalase ('nanozyme') then parenterally injected protect the nigrostriatum in a murine model of Parkinson's disease. Packaging of catalase into block ionomer complex with a synthetic polyelectrolyte block copolymer precludes enzyme degradation in 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.

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 ε-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.

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