(232c) Multi-Component Mass Transfer From a Polymeric Micelle Nanocontainer for Cancer Drug Delivery

Most cancer drug candidates are not water soluble but require carriers such as poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles to enhance their delivery. Experiments by Shin et al. [1] using PEG-b-PLA micelles as vectors for combinations of three hydrophobic cancer drugs (paclitaxel, 17-allylamino-17-demethoxygeldanamycin (17-AAG), and rapamycin) found the delivery half life to be a function of the oil-water partition coefficient in contrast to their assertion that the drug cocktail release rate is diffusion controlled. Here we explain this unexpected, but important, result using a multi-component mass transfer model to estimate the flux of drug delivery. We use linearized theory and a general Fickian mass transfer approach to determine the concentration over time and distance from the micelle center. Different diffusivity models were assessed to determine the optimal diffusion coefficients required to fit the experimental data. Our results are in reasonable agreement with the experimental data, validating the applied methodology. This work provides a sophisticated model of combination drug delivery using polymer micelles and a platform for design of carriers for hydrophobic drug cocktails that will be increasingly important as most new drug candidates for diseases from heart disease to Alzheimer’s are large hydrophobic molecules.

1) Ho-Chul Shin, Adam W. G. Alani, Hyunah Cho, Younsoo Bae, Jill M. Kolesar, and Glen S. Kwon. A 3-in-1 polymeric micelle nanocontainer for poorly water-soluble drugs. Molecular Pharmaceutics, 8(4):1257–1265, 2011.