Journal
NANO RESEARCH
Volume 11, Issue 10, Pages 5689-5703Publisher
TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-018-2069-x
Keywords
polymersome; non-human primate; nanoprecipitation; toxicity; biodistribution
Categories
Funding
- Robert H Lurie Comprehensive Cancer Center of Northwestern University
- NCI CCSG [P30 CA060553]
- Chicago Biomedical Consortium
- Searle Funds at The Chicago Community Trust
- Northwestern University, E.I. DuPont de Nemours Co.
- Dow Chemical Company
- DOE Office of Science by Argonne National Laboratory [06CH11357]
- Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF) [NNCI-1542205]
- MRSEC program [NSF DMR-1121262]
- International Institute for Nanotechnology (IIN)
- Keck Foundation
- State of Illinois, through the IIN
- NSF [CHE-1048773]
- State of Illinois and International Institute for Nanotechnology (IIN) [NCI CA060553]
- Robert H Lurie Comprehensive Cancer Center
Ask authors/readers for more resources
Vesicular nanocarrier formulations confer the ability to deliver hydrophobic and hydrophilic cargos simultaneously to cells of interest in vivo. While liposomal formulations reached the clinic long ago, younger technologies such as polymeric vesicles (polymersomes) have yet to make the transition to clinical approval and use, in part due to difficulties in ensuring their safe and scalable production. In this work, we demonstrate the scalable production of poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-bl-PPS) polymersomes via flash nanoprecipitation, and further show the safe administration of these nanocarriers to mice and non-human primates. In mice, PEG-bl-PPS polymersomes were found to be well tolerated at up to 200 mg/(kg.week). Following the administration of a more relevant 20 mg/(kg.week) dosage in non-human primates, polymersomes were found to associate with numerous phagocytic immune cell populations, including a remarkable 68% of plasmacytoid dendritic cells and > 95% of macrophages in the spleen, while showing no toxicity or abnormalities in the liver, kidney, spleen, or blood. Despite the presence of a dense PEG corona, neither anti-PEG antibodies nor complement activation were detected. This work provides evidence of the translatability of PEG-bl-PPS polymersomes into the clinic for therapeutic applications in humans.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available