期刊
NANOMEDICINE
卷 6, 期 1, 页码 25-42出版社
FUTURE MEDICINE LTD
DOI: 10.2217/NNM.10.129
关键词
blood-brain barrier; catalase; cell-mediated drug delivery; nanozyme; neuroinflammation; Parkinson's disease
资金
- NIH [1RO1 NS057748, 2R01 NS034239, 2R37 NS36126, P01 NS31492, P20RR 15635, P01 MH64570, 5P01 DA028555, P01 NS43985, RR021937]
- Russian Ministry of Science and Education [02.740.11.5232, 11.G4.31.0004]
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR021937, P20RR015635] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [P01MH064570, P30MH062261] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R37NS036126, R01NS070190, P01NS043985, R01NS034239, P01NS031492, R01NS057748, R01NS036126] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [P01DA028555] Funding Source: NIH RePORTER
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. 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 epsilon-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.
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