title: Active Targeted Macrophage-mediated Delivery of Catalase to Affected Brain Regions in Models of Parkinson's Disease.
abstract: We previously demonstrated that monocyte-macrophage based drug delivery can be applied to a spectrum of infectious, neoplastic, and degenerative disorders. In particular, bone marrow-derived macrophages (BMM) loaded with nano formulated catalase, "nanozyme", were shown to attenuate neuro inflammation and nigrostriatal degeneration in rodent models of Parkinson's disease (PD). Nonetheless, the pharmacokinetics and biodistribution of BMM-incorporated nanozyme has not been explored. To this end, we now demonstrate that BMM, serving as a "depot" for nanozyme, increased area under the curve(AUC), half-life, and mean residence time in blood circulation of the protein when compared to the nanozyme administered alone. Accordingly, bioavailability of the nanozyme for the brain, spleen, kidney, and liver was substantially increased. Importantly, nanozyme-loaded BMM targeted diseased sites and improved transport across the blood brain barrier. This was seen specifically in affected brain subregions in models of PD. Engaging natural immune cells such as monocyte-macrophages as drug carriers provides a new perspective for therapeutic delivery for PD and also likely a range of other inflammatory and degenerative diseases.
authors.affiliation: Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zhao
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Haney
authors.forename: Vivek
authors.initials: V
authors.lastname: Mahajan
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Reiner
authors.forename: Anna
authors.initials: A
authors.lastname: Dunaevsky
authors.forename: R Lee
authors.initials: RL
authors.lastname: Mosley
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Elena V
authors.initials: EV
authors.lastname: Batrakova