Systematic Study of Perfluorocarbon Nanoemulsions Stabilized by Polymer Amphiphiles

Abstract

Perfluorocarbon (PFC) nanoemulsions, droplets of fluorous solvent stabilized by surfactants dispersed in water, are simple yet versatile nanomaterials. The orthogonal nature of the fluorous phase promotes the formation of nanoemulsions through a simple, self-assembly process while simultaneously encapsulating fluorous-tagged payloads for various applications. The size, stability, and surface chemistry of PFC nanoemulsions are controlled by the surfactant. Here, we systematically study the effect of the hydrophilic portion of polymer surfactants on PFC nanoemulsions. We find that the hydrophilic block length and identity, the overall polymer hydrophilic/lipophilic balance, and the polymer architecture are all important factors. The ability to modulate these parameters enables control over initial size, stability, payload retention, cellular internalization, and protein adsorption of PFC nanoemulsions. With the insight obtained from this systematic study of polymer amphiphiles stabilizing PFC nanoemulsions, design features required for the optimal material are obtained.

Redox‐Responsive Gene Delivery from Perfluorocarbon Nanoemulsions through Cleavable Poly(2‐oxazoline) Surfactants

“…We have previously developed poly(2‐oxazoline) (POx) block copolymer surfactants capable of stabilizing oil‐in‐water nanoemulsions [18, 19] . These amphiphiles form sub‐200 nm droplets through emulsification involving either PFCs or olive oil as the emulsion core.…”

“…The main challenge with PFC nanoemulsions as delivery vehicles is solubilizing payloads in the fluorous phase. We have successfully encapsulated small molecule fluorophores and therapeutics within PFC nanoemulsions through covalent attachment of fluorous tags [14, 16–19] . Recently, Medina and co‐workers extended the payloads capable of being delivered with PFC nanoemulsions to include proteins by creating a “fluorous mask” around GFP with non‐covalent fluorinated anionic tags [20] .…”

“…The pDNA/ 11 polyplex was then dissolved in a PFC mixture and sonicated (Figure 4 A). Model POx amphiphile poly(2‐ethyl‐2‐oxazoline) 90 ‐ b ‐poly(2‐nonyl‐2‐oxazoline) 10 [19] was solubilized in dimethylformamide and diluted with PBS (pH 7.4) to a loading of 2.8 wt %. This solution was combined with 10 vol % of the PFC/pDNA/ 11 mixture and ultrasonicated.…”

“…We have successfully encapsulated small molecule fluorophores and therapeutics within PFC nanoemulsions through covalent attachment of fluorous tags. [14,[16][17][18][19] Recently, Medina and co-workers extended the payloads capable of being delivered with PFC nanoemulsions to include proteins by creating a "fluorous mask" around GFP with non-covalent fluorinated anionic tags. [20] GFP was then delivered in cells using ultrasound-induced cavitation.…”

“…We have previously developed poly(2-oxazoline) (POx) block copolymer surfactants capable of stabilizing oil-inwater nanoemulsions. [18,19] These amphiphiles form sub-200 nm droplets through emulsification involving either PFCs or olive oil as the emulsion core. We found that a poly(2-methyl-2-oxazoline)-b-poly(2-nonyl-2-oxazoline) (P(MeOx) 30 -b-P(NonOx) 12 , 6, Figure 2 A) diblock copolymer was optimal for emulsions of < 200 nm in size with stability over 60 days.…”