(217cu) The Effects of Protein Deposition and Shear On Polymer Micelle Morphology and Stability

Drug delivery vehicles have shown promise in improving the effectiveness of treatments of certain diseases with cancer being a main focus. In these systems drugs are loaded into the vehicles and the vehicles are then administered to animals, mostly through tail-vein injection. The goal is for the vehicles to avoid healthy areas of the animals and localize only to target areas. The drugs are then released in the target area with the hope of eradicating the tumor cells.

Several major obstacles exist that keep the above sequence of events from occurring seamlessly. The first is the deposition of plasma proteins onto the vehicles. These include immunoglobulins, lipoproteins, complement proteins, and coagulation factors. In addition to alerting the mononuclear phagocyte system (MPS), these factors can destabilize the structural integrity of vehicles – especially those made of amphiphiles like liposomes, micelles, and vesicles.

We monitor the structural integrity of giant worm-like micelles (“filomicelles”) using high-resolution electron microscopy (EM) techniques. After incubation in aqueous media, the ends of degradable filomicelles composed of poly(ethylene glycol) - poly(caprolactone) diblock copolymers start to unwind in EM images whereas non-degradable filomicelles composed of poly(ethylene glycol) - poly(butadiene) diblock copolymers maintain their structural integrity. This result has major implications for the leakage of drugs and dyes from biodegradable drug delivery vehicles.