(341c) Effects of Block Copolymer Properties On Nanoparticle Surface Coverage, Complement Activation, and In Vivo Circulation Half-Times

There has been a dedicated effort in recent decades towards the development of efficient nano carriers that deliver drugs to the majority of tissues.  For passive and active targeting, long circulation times are required, which necessitates that the drug carrier not trigger mechanisms involved in the immune system that are dedicated to the elimination of foreign particles. While it has been established that a poly(ethylene glycol) (PEG) surface coating extends circulation times, the details of polymer surface coverage and chemistry must be investigated to optimize circulation times, permitting passive and active targeting mechanisms.  Rapid precipitation and assembly of nanoparticles and stabilizing block copolymers enables the formation of a PEG corona which is denser than an equilibrium adsorption process permits.  We have compared data from in vivo nanoparticle circulation studies to in vitro complement activation to gain insight on the effects of hydrophobic block chemistry and molecular weight, finding that large crystalline blocks destabilize nanoparticles in the presence of serum proteins and short, amorphous blocks enable enhanced protection and longer circulation times.