In light of research
reporting abnormal pharmacokinetic 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 CD68hi and CD11bhi macrophages
showed similar levels of polymer association, despite CD11bhi 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 cytokines 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 CD68hi 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.