Hyperbranched Poly(2-oxazoline)s and Poly(ethylene glycol): A Structure-Activity Comparison of Biodistribution
- 1 August 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Biomacromolecules
- Vol. 21 (8), 3318-3331
- https://doi.org/10.1021/acs.biomac.0c00765
Abstract
In light of research reporting abnormal pharmaco-kinetic behavior for therapeutics and formulations containing poly(ethylene glycol) (PEG), a renewed emphasis has been placed on exploring alternative surrogate materials and tailoring specific materials to distinct nanomedicine applications. Poly(2-oxazolines) (POx) have shown great promise in this regard; however, a comparison of POx and PEG interactions with components of the immune system is needed to inform on their distinct suitability. Herein, the interaction of isolated immune cells following injection of hyperbranched polymers comprised of PEG or hydrophilic POx macromonomers was determined via flow cytometry. All materials showed similar association with all of the splenic immune cells analyzed. Interestingly, splenic CD68(hi) and CD11b(hi) macrophages showed similar levels of polymer association, despite CD11b(hi) being a smaller population, suggesting CD68 is linked to increased recognition and phagocytosis of these nanomaterials. This is of interest given that CD68 is a scavenger receptor and directly facilitates the clearance of cellular debris and promotion of phagocytosis, as opposed to CD11b, which is associated with the mediating inflammation via the production of cytoldnes as well as complement-mediated uptake of foreign particles. In the liver, PEG and poly(2-methyl oxazoline) hyperbranched polymers showed no discernible differences in their cellular association, while hyperbranched poly(2-ethyl oxazoline) showed increased association with dendrocytes and CD68(hi) macrophages, suggesting that this material exhibited a greater propensity to interact with components of the immune system. This work highlights the importance of how subtle changes in chemical structure can influence the immune response.Funding Information
- National Health and Medical Research Council (APP1054569, APP1099321, APP1148582)
- Australian Research Council (CE140100036, FT190100572, IC170100035, LP150100703)
This publication has 78 references indexed in Scilit:
- The Immunogenicity of Polyethylene Glycol: Facts and FictionPharmaceutical Research, 2013
- Neutrophils and Macrophages: the Main Partners of Phagocyte Cell SystemsFrontiers in Immunology, 2012
- The effect of surface charge on in vivo biodistribution of PEG-oligocholic acid based micellar nanoparticlesBiomaterials, 2011
- Star poly(2-ethyl-2-oxazoline)s-synthesis and thermosensitivityPolymer International, 2011
- Polyoxazoline: Chemistry, Properties, and Applications in Drug DeliveryBioconjugate Chemistry, 2011
- Functional Hyperbranched Polymers: Toward Targeted in Vivo 19F Magnetic Resonance Imaging Using Designed MacromoleculesJournal of the American Chemical Society, 2010
- Lower Critical Solution Temperature Behavior of Comb and Graft Shaped Poly[oligo(2-ethyl-2-oxazoline)methacrylate]sMacromolecules, 2009
- PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent mannerJournal of Controlled Release, 2007
- Antibody against poly(ethylene glycol) adversely affects PEG‐asparaginase therapy in acute lymphoblastic leukemia patientsCancer, 2007
- New Amphipatic Polymer-Lipid Conjugates Forming Long-Circulating Reticuloendothelial System-Evading LiposomesBioconjugate Chemistry, 1994