Biodistribution of Biomimetic Drug Carriers, Mononuclear Cells, and Extracellular Vesicles, in Nonhuman Primates.

Autor: Haney MJ; Center for NanotechFnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.; Eshelman School of Pharmacy, University of North Carolina at Chapel, Hill, Chapel Hill, NC, 27599, USA., Yuan H; Department of Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA., Shipley ST; Division of Comparative Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Wu Z; Department of Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA., Zhao Y; Center for NanotechFnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.; Eshelman School of Pharmacy, University of North Carolina at Chapel, Hill, Chapel Hill, NC, 27599, USA., Pate K; Division of Comparative Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA., Frank JE; Department of Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA., Massoud N; Division of Comparative Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Stewart PW; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Perlmutter JS; School of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Batrakova EV; Center for NanotechFnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.; Eshelman School of Pharmacy, University of North Carolina at Chapel, Hill, Chapel Hill, NC, 27599, USA.
Jazyk: angličtina
Zdroj: Advanced biology [Adv Biol (Weinh)] 2022 Feb; Vol. 6 (2), pp. e2101293. Date of Electronic Publication: 2021 Dec 22.
DOI: 10.1002/adbi.202101293
Abstrakt: Discovery of novel drug delivery systems to the brain remains a key task for successful treatment of neurodegenerative disorders. Herein, the biodistribution of immunocyte-based carriers, peripheral blood mononuclear cells (PBMCs), and monocyte-derived EVs are investigated in adult rhesus macaques using longitudinal PET/MRI imaging. 64 Cu-labeled drug carriers are introduced via different routes of administration: intraperitoneal (IP), intravenous (IV), or intrathecal (IT) injection. Whole body PET/MRI (or PET/CT) images are acquired at 1, 24, and 48 h post injection of 64 Cu-labeled drug carriers, and standardized uptake values (SUV mean and SUV max ) in the main organs are estimated. The brain retention for both types of carriers increases based on route of administration: IP < IV < IT. Importantly, a single IT injection of PBMCs produces higher brain retention compared to IT injection of EVs. In contrast, EVs show superior brain accumulation compared to the cells when administered via IP and IV routes, respectively. Finally, a comprehensive chemistry panel of blood samples demonstrates no cytotoxic effects of either carrier. Overall, living cells and EVs have a great potential to be used for drug delivery to the brain. When identifying the ideal drug carrier, the route of administration could make big differences in CNS drug delivery.
(© 2021 The Authors. Advanced Biology published by Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: