Amphiphilic diblock copolymers are well known to form a variety of supramolecular morphologies – spherical micelles, worm-like micelles, and bilayer vesicles (polymersomes) – that have been studied extensively for drug delivery applications. Previous studies with these polymer-based carriers have shown that their circulation kinetics in vivo can be enhanced with the presence of polyethylene glycol (PEG) on their outer surface. This neutral PEG brush delays the opsonization by serum proteins that allows the body's immune system to recognize and clear the drug carrier from the body. While these carriers have shown promising circulation kinetics (t1/2 ~ 18 hours for 100 nm polymersomes), longer circulation times are certainly possible based on red blood cells with lifetimes of many weeks to months (110 days in humans).

Cell membranes have a glycocalyx with a net negative charge, which motivates studies of polymers other than PEG. The diblock copolymer poly(acrylic acid)-polybutadiene (PAA-PBD) carries a large negative charge, and assemblies of this charged copolymer in water have been shown to undergo morphological phase transitions based on aqueous solution pH and salt concentration. Blends of PAA-PBD and a polymersome-forming PEG-PBD are fully miscible in organic solvent and can be dried to form a homogeneous polymer film. By hydrating this film in aqueous conditions suited to polymersome formation, the surface charge of the resulting polymersomes has been shown to be linearly tunable with the blend fraction of PAA-PBD. By incorporating only a small percentage of PAA-PBD, polymersomes with a dense PEG brush can be made to have a surface charge similar to that of red blood cells. These polymersomes can be sized down to a diameter of 100 nm, and studies in blood plasma have demonstrated that these anionic nano-polymersomes are stable at physiological conditions for at least 24 hours. Ongoing experiments examine the in vivo stability and circulation.