Thermodynamic and kinetic stability of DSPE-PEG(2000) micelles in the presence of bovine serum albumin

This work investigated the stability of DSPE-PEG(2000) micelles in the presence of bovine serum albumin (BSA). DSPE-PEG(2000) was found to exist in equilibrium among monomeric, micellar, and BSA-bound states, and this equilibrium shifted toward the BSA-bound state when the temperature increased from 20 to 37°C. The micellar state is thermodynamically unstable at both temperatures when the concentration of BSA approaches that of DSPE-PEG(2000), and micelle breakup occurs with a first-order time constant of 130±9 min at 20°C and 7.8±1.6 min at 37°C. Thus, previous targeting experiments that demonstrate synergistic effects in multiply functionalized DSPE-PEG(2000) micelles are likely due to targeting that occurs on a timescale faster than that of micelle breakup. Micelle breakup was limited by diffusion at 20°C whereas at 37°C monomer desorption from the micelle was the rate-limiting step. These findings give clear guidance concerning the lifetimes of micelles that may be used as diagnostic and therapeutic nanoparticles.