Morphology Dependent Hydrophobic Drug Partitioning In PEO-PCL Micelles Investigated with Coarse-Grained Molecular Dynamics

Atomistically accurate, coarse-grained (CG) polymer models have been developed and studied for poly(ethylene oxide) -poly(caprolactone) (PEO-PCL), with molecular dynamics simulations comparing well with experimental phase behavior.  The anti-cancer drug paclitaxel is also being CG'd with intramolecular interactions again obtained from all-atomistic molecular dynamics.  Solubility of paclitaxel indicates that partitioning of the drug is dependent on micellar morphology.  Utilizing free energy techniques, it is found that the hydrophobic drug possesses a greater partitioning in a worm micelle morphology of the same diblock weight than a spherical micelle morphology.  These findings are consistent with previously found experimental results from the Discher laboratory.  Moreover, at larger loading concentrations, the taxol-PCL and taxol-taxol interactions significantly shift the micellar density profile, showing increased interactions with the PEO, which may be an explanation for the phenomena of ‘burst release.’