Year: 2010
Type: article
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 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 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. CONCLUSION: Nanozymes with polyethyleneimine- and poly(L-lysine)(10)-poly(ethylene glycol) provided the best protection of enzymatic activity for cell-mediated drug delivery.
Source: Nanomedicine
DOI: 10.2217/nnm.10.129
Authors: 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
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
Awards: G1024824085, G1439906246, G1544212162, G1679034498, Nebraska Center for Virology, G2117496444, G2244085143, Blood Brain Barrier Physiology and HIV Dementia, G2585785709, G3117926025, G3283595100, G4177415819, G4225214907, G526054707, G54233322, G574326724, G7989492622, G8066218739, G9000013815, G9000020704, G9000035232, G9000101189, G9000123435, Neuroprotective Immunity and HIV Dementia, G9000230184
OpenAlex ID: W2154241043