Benchmarking Bicontinuous Nanospheres against Polymersomes for in Vivo Biodistribution and Dual Intracellular Delivery of Lipophilic and Water-Soluble Payloads
Bicontinuous nanospheres (BCNs) are polymeric analogs to lipid cubosomes, possessing cubic liquid crystalline phases with high internal surface area, aqueous channels for loading hydrophilic molecules, and high hydrophobic volume for lipophilic payloads. Primarily due to difficulties in scalable and consistent fabrication, neither controlled delivery of payloads via BCNs nor their organ or cellular biodistributions following in vivo administration have been demonstrated or characterized. We have recently validated flash nanoprecipitation as a rapid method of assembling uniform monodisperse 200–300 nm diameter BCNs from poly(ethylene glycol)-$$b$$-poly(propylene sulfide) (PEG-$$b$$-PPS) co-polymers. In this work, we compare these BCNs both in vitro and in vivo to 100 nm PEG-$$b$$-PPS polymersomes (PSs), which have been well characterized as nanocarriers for controlled delivery applications. Using a small molecule fluorophore and a fluorescently tagged protein as respective lipophilic and water-soluble model cargos, we demonstrate that BCNs can achieve significantly higher encapsulation efficiencies for both payloads on a per unit mass basis. At time points of 4 and 24 h after intravenous administration to mice, we found significant differences in organ-level uptake between BCNs and PSs, with BCNs showing reduced accumulation in the liver and increased uptake in the spleen. Despite these organ-level differences, BCNs and PSs displayed strikingly similar uptake profiles by immune cell populations in vitro and in the liver, spleen, and blood, as assayed by flow cytometry. In conclusion, we have found PEG-$$b$$-PPS BCNs to be well suited for dual loading and delivery of molecular payloads, with a favorable organ biodistribution and high cell uptake by therapeutically relevant immune cell populations.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- Chicago Biomedical Consortium; National Cancer Institute (NCI); Northwestern University; E.I. DuPont de Nemours & Co.; The Dow Chemical Company; USDOE Office of Science (SC); National Science Foundation (NSF); International Institute for Nanotechnology (IIN); Keck Foundation; State of Illinois; National Institutes of Health (NIH)
- Grant/Contract Number:
- AC02-06CH11357; NCI CA060553; NCI CCSG P30 CA060553; 1453576; 1DP2HL132390-01
- OSTI ID:
- 1479021
- Journal Information:
- ACS Applied Materials and Interfaces, Vol. 10, Issue 40; ISSN 1944-8244
- Publisher:
- American Chemical Society (ACS)Copyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
Web of Science
On the advancement of polymeric bicontinuous nanospheres toward biomedical applications
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journal | January 2019 |
Bilayered membranes of Janus dendrimers with hybrid hydrogenated and fluorinated dendrons: microstructures and coassembly with lipids
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journal | January 2019 |
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